data_4966 ####################### # Entry information # ####################### save_entry_information _Saveframe_category entry_information _Entry_title ; 1H and 13C Chemical Shift Assignments for Cardiotoxin A3 from Naja Atra at Neutral pH ; _BMRB_accession_number 4966 _BMRB_flat_file_name bmr4966.str _Entry_type original _Submission_date 2001-03-06 _Accession_date 2001-03-06 _Entry_origination author _NMR_STAR_version 2.1.1 _Experimental_method NMR _Details . loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Sue Shih-Che . . 2 Jarrell Harold C. . 3 Brisson Jean-Robert . . 4 Wu Wen-guey . . stop_ loop_ _Saveframe_category_type _Saveframe_category_type_count assigned_chemical_shifts 1 stop_ loop_ _Data_type _Data_type_count "1H chemical shifts" 366 "13C chemical shifts" 59 stop_ loop_ _Revision_date _Revision_keyword _Revision_author _Revision_detail 2001-03-09 original BMRB . stop_ _Original_release_date 2001-03-06 save_ ############################# # Citation for this entry # ############################# save_entry_citation _Saveframe_category entry_citation _Citation_full . _Citation_title ; Dynamic Characterization of the Water binding loop in the P-type Cardiotoxin: Implication for the role of the bound Water Molecule ; _Citation_status published _Citation_type journal _CAS_abstract_code . _MEDLINE_UI_code 21526408 _PubMed_ID 11669614 loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Sue Shih-Che . . 2 Jarrell Harold C. . 3 Brisson Jean-Robert . . 4 Wu Wen-guey . . stop_ _Journal_abbreviation Biochemistry _Journal_volume 40 _Journal_issue 43 _Journal_CSD . _Book_chapter_title . _Book_volume . _Book_series . _Book_ISBN . _Conference_state_province . _Conference_abstract_number . _Page_first 12782 _Page_last 12794 _Year 2001 _Details ; This paper describes a comprehensive NMR analysis of the structure and dynamics of P-type cardiotoxin and its bound water by using triple-quantum 17O NMR, NOE/ROE 2D NMR, and 13C T1 relaxation. ; loop_ _Keyword '13C relaxation' '17O NMR' Cardiotoxin 'bound water molecule' 'order parameter' 'residence time' 'triple-quantum filtered' 'water binding loop' stop_ save_ ####################################### # Cited references within the entry # ####################################### save_ref_1 _Saveframe_category citation _Citation_full ; Bhaskaran R, Huang CC, Chang DK, Yu C. Cardiotoxin III from the Taiwan cobra (Naja naja atra). Determination of structure in solution and comparison with short neurotoxins. J Mol Biol. 1994 Jan 28;235(4):1291-301. ; _Citation_title ; Cardiotoxin III from the Taiwan cobra (Naja naja atra). Determination of structure in solution and comparison with short neurotoxins. ; _Citation_status published _Citation_type journal _CAS_abstract_code . _MEDLINE_UI_code . _PubMed_ID 8308891 loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Bhaskaran R . . 2 Huang 'C C' C. . 3 Chang 'D K' K. . 4 Yu C . . stop_ _Journal_abbreviation 'J. Mol. Biol.' _Journal_name_full 'Journal of molecular biology' _Journal_volume 235 _Journal_issue 4 _Journal_CSD . _Book_title . _Book_chapter_title . _Book_volume . _Book_series . _Book_publisher . _Book_publisher_city . _Book_ISBN . _Conference_title . _Conference_site . _Conference_state_province . _Conference_country . _Conference_start_date . _Conference_end_date . _Conference_abstract_number . _Thesis_institution . _Thesis_institution_city . _Thesis_institution_country . _Page_first 1291 _Page_last 1301 _Year 1994 _Details ; The structure in solution of cardiotoxin III, a membrane toxin purified from the venom of the Taiwan cobra, Naja naja atra, is reported. Sequence-specific assignment of 1H-NMR lines was completed and the NMR data show the presence of a triple and a double-stranded antiparallel beta-sheet. Many NOE cross peaks identified in NOESY spectra were applied as distance constraints based on a hybrid distance geometry/dynamical simulated annealing technique; 20 structures were found within a single family. The average value of atomic RMS differences between the 20 structures and their geometric mean is 0.087 nm for the backbone atoms and 0.152 nm for all heavy atoms; they are 0.055 nm and 0.12 nm, respectively for the segments of secondary structure. In these selected structures the backbone of the polypeptide chain folds such that five strands emerge from a globular head. Three major loops link these strands to form a double and a triple-stranded antiparallel beta-sheet. Comparison of the structures of the toxin in solution with the X-ray crystal structure of its homologous protein, cardiotoxin V4II from Naja mossambica mossambica, showed good agreement between the structures except at segments of the turns. As the functions of short neurotoxins and cardiotoxins are distinct, despite their similar secondary structural patterns and tertiary folding, a comparative analysis has been carried out between cardiotoxin III and short neurotoxins of known structures. We discuss their structural features in order to clarify relationships between their structure and function. ; save_ save_ref_2 _Saveframe_category citation _Citation_full ; Chiang CM, Chang SL, Lin HJ, Wu WG. The role of acidic amino acid residues in the structural stability of snake cardiotoxins. Biochemistry. 1996 Jul 16;35(28):9177-86. ; _Citation_title ; The role of acidic amino acid residues in the structural stability of snake cardiotoxins. ; _Citation_status published _Citation_type journal _CAS_abstract_code . _MEDLINE_UI_code . _PubMed_ID 8703923 loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Chiang 'C M' M. . 2 Chang 'S L' L. . 3 Lin 'H J' J. . 4 Wu 'W G' G. . stop_ _Journal_abbreviation Biochemistry _Journal_name_full Biochemistry _Journal_volume 35 _Journal_issue 28 _Journal_CSD . _Book_title . _Book_chapter_title . _Book_volume . _Book_series . _Book_publisher . _Book_publisher_city . _Book_ISBN . _Conference_title . _Conference_site . _Conference_state_province . _Conference_country . _Conference_start_date . _Conference_end_date . _Conference_abstract_number . _Thesis_institution . _Thesis_institution_city . _Thesis_institution_country . _Page_first 9177 _Page_last 9186 _Year 1996 _Details ; We have recently shown that membrane-related activities of cardiotoxin V from Naja naja atra (CTX A5) are diminished at acidic pH although the overall beta-sheet structure of the molecule is maintained. In order to understand more about the mechanism of inactivation of CTX at acidic pH, we studied the effect of pH and denaturing reagents on the structural stability of CTX. We found, first, pH-induced structural transitions occurred in CTX A5 at two pH values as judged by the CD ellipticity around 195 nm: an increase in the beta-sheet content occurred around pH 4 and followed by a decrease, therein, around pH 2. The pKa of three acidic amino acid residues in CTX A5, i.e., Glu-17, Asp-42, and Asp-59, were determined to be 4.0, 3.2, and below 2.3, respectively, by NMR spectroscopy. The low pKa value of Asp-59 implies salt bridge formation between Lys-2 and Asp-59. Thus, electrostatic interaction may stabilize the three loop structure in addition to the hydrogen bonds between N- and C-termini of CTX molecule. Second, 2,2,2-trifluoroethanol (TFE) and guanidinium chloride (GdmHCI) were found to induce alpha-helical and random coil formation, respectively, in CTX A5 and eight other beta-sheet CTXs. Comparison of the relative potencies of TFE and GdmHCI to induce structural changes suggests that the amino acid residue located at position 17 plays a role in the structural stability. Specifically, CTXs containing negatively charged Glu-17 are least stable. It is suggested that Glu-17 may perturb the interaction between Lys-2 and Asp-59, and thus the overall stability of beta-sheet, in the presence of denaturing reagent. In conclusion, the perturbed structural stability of CTXs may partially explain the lower activity CTX exhibits at acidic pH. A structural model to account for the unfolding and refolding of CTX molecules without the breaking of disulfide bonds is also proposed. ; save_ ################################## # Molecular system description # ################################## save_system_CTX_A3 _Saveframe_category molecular_system _Mol_system_name 'Cardiotoxin A3' _Abbreviation_common 'CTX A3' _Enzyme_commission_number . loop_ _Mol_system_component_name _Mol_label 'cardiotoxin A3' $CTX_A3 stop_ _System_molecular_weight . _System_physical_state native _System_oligomer_state monomer _System_paramagnetic no _System_thiol_state 'all disulfide bound' loop_ _Biological_function 'depolarization of muscular cell' hemolysis 'heparin binding protien' 'membrane binding protein' 'protein with one bound water' stop_ _Database_query_date . _Details . save_ ######################## # Monomeric polymers # ######################## save_CTX_A3 _Saveframe_category monomeric_polymer _Mol_type polymer _Mol_polymer_class protein _Name_common 'Cardiotoxin A3' _Abbreviation_common 'CTX A3' _Molecular_mass 6741 _Mol_thiol_state 'all disulfide bound' _Details . ############################## # Polymer residue sequence # ############################## _Residue_count 60 _Mol_residue_sequence ; LKCNKLVPLFYKTCPAGKNL CYKMFMVATPKVPVKRGCID VCPKSSLLVKYVCCNTDRCN ; loop_ _Residue_seq_code _Residue_label 1 LEU 2 LYS 3 CYS 4 ASN 5 LYS 6 LEU 7 VAL 8 PRO 9 LEU 10 PHE 11 TYR 12 LYS 13 THR 14 CYS 15 PRO 16 ALA 17 GLY 18 LYS 19 ASN 20 LEU 21 CYS 22 TYR 23 LYS 24 MET 25 PHE 26 MET 27 VAL 28 ALA 29 THR 30 PRO 31 LYS 32 VAL 33 PRO 34 VAL 35 LYS 36 ARG 37 GLY 38 CYS 39 ILE 40 ASP 41 VAL 42 CYS 43 PRO 44 LYS 45 SER 46 SER 47 LEU 48 LEU 49 VAL 50 LYS 51 TYR 52 VAL 53 CYS 54 CYS 55 ASN 56 THR 57 ASP 58 ARG 59 CYS 60 ASN stop_ _Sequence_homology_query_date 2008-08-19 _Sequence_homology_query_revised_last_date 2008-08-19 loop_ _Database_name _Database_accession_code _Database_entry_mol_name _Sequence_query_to_submitted_percentage _Sequence_subject_length _Sequence_identity _Sequence_positive _Sequence_homology_expectation_value BMRB 15305 cardiotoxin_A3 100.00 60 100.00 100.00 9.64e-26 PDB 1H0J 'Structural Basis Of The Membrane-Induced Cardiotoxin A3 Oligomerization' 100.00 60 100.00 100.00 9.64e-26 PDB 1I02 'Nmr Structure Of Ctx A3 At Neutral Ph (20 Structures)' 100.00 60 100.00 100.00 9.64e-26 PDB 1XT3 'Structure Basis Of Venom Citrate-Dependent Heparin Sulfate- Mediated Cell Surface Retention Of Cobra Cardiotoxin A3' 100.00 60 100.00 100.00 9.64e-26 PDB 2BHI 'Crystal Structure Of Taiwan Cobra Cardiotoxin A3 Complexed With Sulfogalactoceramide' 100.00 60 100.00 100.00 9.64e-26 PDB 2CRS 'Cardiotoxin Iii From Taiwan Cobra (Naja Naja Atra) Determination Of Structure In Solution And Comparison With Short Neurotoxins' 100.00 60 100.00 100.00 9.64e-26 PDB 2CRT 'Cardiotoxin Iii From Taiwan Cobra (Naja Naja Atra) Determination Of Structure In Solution And Comparison With Short Neurotoxins' 100.00 60 100.00 100.00 9.64e-26 EMBL CAA07686 'cardiotoxin 3 precursor protein [Naja atra]' 100.00 81 100.00 100.00 3.15e-26 EMBL CAA90963 'cardiotoxin 3 [Naja naja]' 100.00 81 98.33 98.33 3.32e-25 EMBL CAB42053 'cardiotoxin-31 [Naja atra]' 100.00 81 98.33 100.00 9.41e-26 EMBL CAB42055 'cardiotoxin-3 [Naja atra]' 100.00 81 100.00 100.00 2.54e-26 GenBank AAA49386 cardiotoxin 100.00 81 100.00 100.00 2.37e-26 GenBank AAB01541 'cardiotoxin III' 100.00 81 100.00 100.00 3.15e-26 GenBank AAB18382 "cardiotoxin 3' [Naja atra]" 100.00 81 100.00 100.00 3.15e-26 GenBank AAB18383 'cardiotoxin 3a [Naja atra]' 100.00 81 98.33 100.00 9.41e-26 GenBank AAB25733 'cardiotoxin isoform 3, cytotoxin isoform 3, CTX-3 [Naja naja=Formosan cobra, ssp. atra, venom, Peptide, 60 aa]' 100.00 60 100.00 100.00 9.64e-26 PIR JK0222 'cytotoxin 10 - monocled cobra' 100.00 60 100.00 100.00 9.64e-26 PRF 0406231A toxin,cardio 100.00 60 100.00 100.00 9.64e-26 PRF 2207174B cardiotoxin:ISOTYPE=III 100.00 81 98.33 98.33 3.32e-25 SWISS-PROT O93471 'Cardiotoxin-1 precursor (CTX-1) (Ctx1)' 100.00 81 98.33 100.00 8.23e-26 SWISS-PROT O93473 'Cardiotoxin-4a precursor (CTX-4a) (Ctx4a)' 100.00 81 98.33 98.33 1.16e-25 SWISS-PROT P60301 'Cardiotoxin-A3 precursor (CTX-A3) (Cardiotoxin 3) (CTX-3) (Cardiotoxin analog III) (CTX III) (Cytotoxin-3)' 100.00 81 100.00 100.00 3.15e-26 SWISS-PROT P60302 'Cardiotoxin-3 precursor (CTX-3) (Ctx3)' 100.00 81 100.00 100.00 3.15e-26 SWISS-PROT P60303 'Cytotoxin-4 precursor (Cytotoxin IV)' 100.00 81 100.00 100.00 3.15e-26 stop_ save_ #################### # Natural source # #################### save_natural_source _Saveframe_category natural_source loop_ _Mol_label _Organism_name_common _NCBI_taxonomy_ID _Superkingdom _Kingdom _Genus _Species _Secretion _Details $CTX_A3 'Taiwan cobra' 8656 Eukaryota Metazoa cobra 'naja atra' venom ; Cobra Venom were purchased from Sigma. Further purification by open column and HPLC was proceeded to get pure cardiotoxin A3 compound. ; stop_ save_ ######################### # Experimental source # ######################### save_experimental_source _Saveframe_category experimental_source loop_ _Mol_label _Production_method _Host_organism_name_common _Genus _Species _Strain _Vector_name _Details $CTX_A3 'purified from the natural source' . . . . . 'purified from cobra venom' stop_ save_ ##################################### # Sample contents and methodology # ##################################### ######################## # Sample description # ######################## save_sample_1 _Saveframe_category sample _Sample_type solution _Details '10mM phosphate buffer was added to maintain the pH value at 6.0.' loop_ _Mol_label _Concentration_value _Concentration_value_units _Isotopic_labeling $CTX_A3 5 mM . 'phosphate buffer' 10 mM . stop_ save_ ############################ # Computer software used # ############################ save_XWINNMR _Saveframe_category software _Name XWINNMR _Version 2.01 _Details . save_ ######################### # Experimental detail # ######################### ################################## # NMR Spectrometer definitions # ################################## save_NMR_spectrometer_1 _Saveframe_category NMR_spectrometer _Manufacturer BRUKER _Model DRX _Field_strength 600 _Details . save_ save_NMR_spectrometer_2 _Saveframe_category NMR_spectrometer _Manufacturer BRUKER _Model DMX _Field_strength 500 _Details . save_ ############################# # NMR applied experiments # ############################# save_COSY_1 _Saveframe_category NMR_applied_experiment _Experiment_name COSY _Sample_label . save_ save_NOESY_2 _Saveframe_category NMR_applied_experiment _Experiment_name NOESY _Sample_label . save_ save_TOCSY_3 _Saveframe_category NMR_applied_experiment _Experiment_name TOCSY _Sample_label . save_ save_HSQC_4 _Saveframe_category NMR_applied_experiment _Experiment_name HSQC _Sample_label . save_ ####################### # Sample conditions # ####################### save_CTX_A3_condition _Saveframe_category sample_conditions _Details ; There is no indication of protein aggregation or degradation as judged by the 1H NMR spectral quailty during the experimental (25C, up to week) and storage time (4C, up to months). The assignments of 13C have been collected from the natural abundance nucleii. ; loop_ _Variable_type _Variable_value _Variable_value_error _Variable_value_units 'ionic strength' 0.03 0.005 M pH 5.96 0.05 n/a pressure 1.013 . atm temperature 300 0.5 K stop_ save_ #################### # NMR parameters # #################### ############################## # Assigned chemical shifts # ############################## ################################ # Chemical shift referencing # ################################ save_chemical_shift_reference _Saveframe_category chemical_shift_reference _Details . loop_ _Mol_common_name _Atom_type _Atom_isotope_number _Atom_group _Chem_shift_units _Chem_shift_value _Reference_method _Reference_type _External_reference_sample_geometry _External_reference_location _External_reference_axis _Indirect_shift_ratio DSS C 13 'methyl protons' ppm 0.0 . indirect . . . 0.251449530 DSS H 1 'methyl protons' ppm 0.0 internal direct . . . 1.0 stop_ save_ ################################### # Assigned chemical shift lists # ################################### ################################################################### # Chemical Shift Ambiguity Index Value Definitions # # # # The values other than 1 are used for those atoms with different # # chemical shifts that cannot be assigned to stereospecific atoms # # or to specific residues or chains. # # # # Index Value Definition # # # # 1 Unique (including isolated methyl protons, # # geminal atoms, and geminal methyl # # groups with identical chemical shifts) # # (e.g. ILE HD11, HD12, HD13 protons) # # 2 Ambiguity of geminal atoms or geminal methyl # # proton groups (e.g. ASP HB2 and HB3 # # protons, LEU CD1 and CD2 carbons, or # # LEU HD11, HD12, HD13 and HD21, HD22, # # HD23 methyl protons) # # 3 Aromatic atoms on opposite sides of # # symmetrical rings (e.g. TYR HE1 and HE2 # # protons) # # 4 Intraresidue ambiguities (e.g. LYS HG and # # HD protons or TRP HZ2 and HZ3 protons) # # 5 Interresidue ambiguities (LYS 12 vs. LYS 27) # # 6 Intermolecular ambiguities (e.g. ASP 31 CA # # in monomer 1 and ASP 31 CA in monomer 2 # # of an asymmetrical homodimer, duplex # # DNA assignments, or other assignments # # that may apply to atoms in one or more # # molecule in the molecular assembly) # # 9 Ambiguous, specific ambiguity not defined # # # ################################################################### save_shift_set_1 _Saveframe_category assigned_chemical_shifts _Details ; The chemical Shift of Cardiotoxin A3 at pH 3.0 have been determinted in 1994. But it was later demonstrated that the assignments were based on at least 9 wrongly assigned signals out of the 60 amino acid residues. The correct assignment of all proton resonance were achieved now at pH 6.0 and 27C. ; loop_ _Experiment_label COSY NOESY TOCSY HSQC stop_ loop_ _Sample_label $sample_1 stop_ _Sample_conditions_label $CTX_A3_condition _Chem_shift_reference_set_label $chemical_shift_reference _Mol_system_component_name 'cardiotoxin A3' _Text_data_format . _Text_data . loop_ _Atom_shift_assign_ID _Residue_author_seq_code _Residue_seq_code _Residue_label _Atom_name _Atom_type _Chem_shift_value _Chem_shift_value_error _Chem_shift_ambiguity_code 1 . 1 LEU HA H 4.175 0.01 1 2 . 1 LEU HB2 H 1.595 0.01 1 3 . 1 LEU HB3 H 1.536 0.01 1 4 . 1 LEU HG H 1.580 0.01 1 5 . 1 LEU HD1 H 0.844 0.01 2 6 . 1 LEU HD2 H 0.777 0.01 2 7 . 1 LEU CA C 52.260 0.15 1 8 . 2 LYS H H 8.638 0.01 1 9 . 2 LYS HA H 5.483 0.01 1 10 . 2 LYS HB2 H 1.417 0.01 1 11 . 2 LYS HB3 H 1.417 0.01 1 12 . 2 LYS HG2 H 1.255 0.01 1 13 . 2 LYS HG3 H 1.255 0.01 1 14 . 2 LYS HE2 H 2.864 0.01 1 15 . 2 LYS HE3 H 2.864 0.01 1 16 . 2 LYS CA C 51.867 0.15 1 17 . 3 CYS H H 8.861 0.01 1 18 . 3 CYS HA H 5.164 0.01 1 19 . 3 CYS HB2 H 2.867 0.01 2 20 . 3 CYS HB3 H 2.470 0.01 2 21 . 3 CYS CA C 49.495 0.15 1 22 . 4 ASN H H 9.676 0.01 1 23 . 4 ASN HA H 5.077 0.01 1 24 . 4 ASN HB2 H 2.771 0.01 2 25 . 4 ASN HB3 H 2.325 0.01 2 26 . 4 ASN HD21 H 7.711 0.01 2 27 . 4 ASN HD22 H 6.557 0.01 2 28 . 4 ASN CA C 52.225 0.15 1 29 . 5 LYS H H 8.009 0.01 1 30 . 5 LYS HA H 4.266 0.01 1 31 . 5 LYS HB2 H 1.620 0.01 1 32 . 5 LYS HB3 H 1.620 0.01 1 33 . 5 LYS HG2 H 1.401 0.01 2 34 . 5 LYS HG3 H 1.261 0.01 2 35 . 5 LYS HD2 H 2.206 0.01 1 36 . 5 LYS HD3 H 2.206 0.01 1 37 . 5 LYS HE2 H 2.919 0.01 1 38 . 5 LYS HE3 H 2.919 0.01 1 39 . 5 LYS CA C 52.828 0.15 1 40 . 6 LEU H H 8.338 0.01 1 41 . 6 LEU HA H 3.677 0.01 1 42 . 6 LEU HB2 H 1.672 0.01 2 43 . 6 LEU HB3 H 1.597 0.01 2 44 . 6 LEU HG H 1.828 0.01 1 45 . 6 LEU HD1 H 0.876 0.01 1 46 . 6 LEU HD2 H 0.720 0.01 1 47 . 6 LEU CA C 56.869 0.15 1 48 . 7 VAL H H 7.654 0.01 1 49 . 7 VAL HA H 4.422 0.01 1 50 . 7 VAL HB H 2.276 0.01 1 51 . 7 VAL HG1 H 1.053 0.01 1 52 . 7 VAL HG2 H 1.053 0.01 1 53 . 7 VAL CA C 57.482 0.15 1 54 . 8 PRO HA H 4.544 0.01 1 55 . 8 PRO HB2 H 2.173 0.01 2 56 . 8 PRO HB3 H 1.984 0.01 2 57 . 8 PRO HG2 H 1.842 0.01 1 58 . 8 PRO HG3 H 1.842 0.01 1 59 . 8 PRO HD2 H 4.052 0.01 2 60 . 8 PRO HD3 H 3.845 0.01 2 61 . 8 PRO CA C 63.358 0.15 1 62 . 9 LEU H H 6.625 0.01 1 63 . 9 LEU HA H 3.959 0.01 1 64 . 9 LEU HB2 H 1.033 0.01 1 65 . 9 LEU HB3 H 1.033 0.01 1 66 . 9 LEU HG H 1.333 0.01 1 67 . 9 LEU HD1 H 0.757 0.01 2 68 . 9 LEU HD2 H 0.719 0.01 2 69 . 9 LEU CA C 54.089 0.15 1 70 . 10 PHE H H 8.139 0.01 1 71 . 10 PHE HA H 4.858 0.01 1 72 . 10 PHE HB2 H 3.228 0.01 2 73 . 10 PHE HB3 H 2.858 0.01 2 74 . 10 PHE HD1 H 7.289 0.01 1 75 . 10 PHE HD2 H 7.289 0.01 1 76 . 10 PHE HE1 H 7.352 0.01 1 77 . 10 PHE HE2 H 7.352 0.01 1 78 . 10 PHE HZ H 7.324 0.01 1 79 . 10 PHE CA C 53.465 0.15 1 80 . 11 TYR H H 8.206 0.01 1 81 . 11 TYR HA H 5.443 0.01 1 82 . 11 TYR HB2 H 2.928 0.01 2 83 . 11 TYR HB3 H 2.686 0.01 2 84 . 11 TYR HD1 H 6.750 0.01 1 85 . 11 TYR HD2 H 6.750 0.01 1 86 . 11 TYR HE1 H 6.806 0.01 1 87 . 11 TYR HE2 H 6.806 0.01 1 88 . 11 TYR CA C 53.309 0.15 1 89 . 12 LYS H H 9.085 0.01 1 90 . 12 LYS HA H 4.829 0.01 1 91 . 12 LYS HB2 H 1.707 0.01 1 92 . 12 LYS HB3 H 1.707 0.01 1 93 . 12 LYS HG2 H 1.384 0.01 2 94 . 12 LYS HG3 H 1.196 0.01 2 95 . 12 LYS HD2 H 1.859 0.01 1 96 . 12 LYS HD3 H 1.859 0.01 1 97 . 12 LYS CA C 51.549 0.15 1 98 . 13 THR H H 8.869 0.01 1 99 . 13 THR HA H 4.712 0.01 1 100 . 13 THR HB H 4.072 0.01 1 101 . 13 THR HG2 H 1.277 0.01 1 102 . 13 THR CA C 60.720 0.15 1 103 . 14 CYS H H 9.179 0.01 1 104 . 14 CYS HA H 4.995 0.01 1 105 . 14 CYS HB2 H 3.549 0.01 2 106 . 14 CYS HB3 H 2.835 0.01 2 107 . 14 CYS CA C 49.552 0.15 1 108 . 15 PRO HA H 4.635 0.01 1 109 . 15 PRO HB2 H 2.419 0.01 2 110 . 15 PRO HB3 H 2.194 0.01 2 111 . 15 PRO HG2 H 1.982 0.01 2 112 . 15 PRO HG3 H 1.903 0.01 2 113 . 15 PRO HD2 H 3.458 0.01 2 114 . 15 PRO HD3 H 4.106 0.01 2 115 . 15 PRO CA C 59.919 0.15 1 116 . 16 ALA H H 8.473 0.01 1 117 . 16 ALA HA H 4.121 0.01 1 118 . 16 ALA HB H 1.380 0.01 1 119 . 16 ALA CA C 51.467 0.15 1 120 . 17 GLY H H 8.799 0.01 1 121 . 17 GLY HA2 H 4.272 0.01 2 122 . 17 GLY HA3 H 3.675 0.01 2 123 . 17 GLY CA C 42.586 0.15 1 124 . 18 LYS H H 7.589 0.01 1 125 . 18 LYS HA H 4.288 0.01 1 126 . 18 LYS HB2 H 1.381 0.01 1 127 . 18 LYS HB3 H 1.381 0.01 1 128 . 18 LYS HG2 H 1.060 0.01 1 129 . 18 LYS HG3 H 1.060 0.01 1 130 . 18 LYS HD2 H 1.919 0.01 1 131 . 18 LYS HD3 H 1.919 0.01 1 132 . 18 LYS HE2 H 2.958 0.01 1 133 . 18 LYS HE3 H 2.958 0.01 1 134 . 18 LYS CA C 53.416 0.15 1 135 . 19 ASN H H 7.946 0.01 1 136 . 19 ASN HA H 4.958 0.01 1 137 . 19 ASN HB2 H 3.029 0.01 2 138 . 19 ASN HB3 H 2.647 0.01 2 139 . 19 ASN HD21 H 7.522 0.01 2 140 . 19 ASN HD22 H 6.986 0.01 2 141 . 19 ASN CA C 50.709 0.15 1 142 . 20 LEU H H 8.225 0.01 1 143 . 20 LEU HA H 4.852 0.01 1 144 . 20 LEU HB2 H 1.712 0.01 2 145 . 20 LEU HB3 H 1.527 0.01 2 146 . 20 LEU HG H 1.378 0.01 1 147 . 20 LEU HD1 H 0.880 0.01 2 148 . 20 LEU HD2 H 0.736 0.01 2 149 . 21 CYS H H 9.050 0.01 1 150 . 21 CYS HA H 6.133 0.01 1 151 . 21 CYS HB2 H 3.054 0.01 2 152 . 21 CYS HB3 H 2.982 0.01 2 153 . 21 CYS CA C 49.516 0.15 1 154 . 22 TYR H H 8.960 0.01 1 155 . 22 TYR HA H 6.099 0.01 1 156 . 22 TYR HB2 H 3.114 0.01 2 157 . 22 TYR HB3 H 2.947 0.01 2 158 . 22 TYR HD1 H 6.624 0.01 1 159 . 22 TYR HD2 H 6.624 0.01 1 160 . 22 TYR HE1 H 6.733 0.01 1 161 . 22 TYR HE2 H 6.733 0.01 1 162 . 22 TYR CA C 53.829 0.15 1 163 . 23 LYS H H 9.080 0.01 1 164 . 23 LYS HA H 4.948 0.01 1 165 . 23 LYS HB2 H 1.710 0.01 1 166 . 23 LYS HB3 H 1.710 0.01 1 167 . 23 LYS HG2 H 1.512 0.01 1 168 . 23 LYS HG3 H 1.512 0.01 1 169 . 23 LYS HD2 H 1.854 0.01 1 170 . 23 LYS HD3 H 1.854 0.01 1 171 . 23 LYS CA C 52.981 0.15 1 172 . 24 MET H H 8.460 0.01 1 173 . 24 MET HA H 5.229 0.01 1 174 . 24 MET HB2 H 1.798 0.01 2 175 . 24 MET HB3 H 1.621 0.01 2 176 . 24 MET HG2 H 1.346 0.01 1 177 . 24 MET HG3 H 1.346 0.01 1 178 . 24 MET CA C 51.324 0.15 1 179 . 25 PHE H H 9.095 0.01 1 180 . 25 PHE HA H 4.943 0.01 1 181 . 25 PHE HB2 H 2.902 0.01 1 182 . 25 PHE HB3 H 2.902 0.01 1 183 . 25 PHE HD1 H 6.907 0.01 1 184 . 25 PHE HD2 H 6.907 0.01 1 185 . 25 PHE HE1 H 7.108 0.01 1 186 . 25 PHE HE2 H 7.108 0.01 1 187 . 25 PHE HZ H 7.236 0.01 1 188 . 25 PHE CA C 53.575 0.15 1 189 . 26 MET H H 9.432 0.01 1 190 . 26 MET HA H 5.106 0.01 1 191 . 26 MET HB2 H 2.273 0.01 2 192 . 26 MET HB3 H 2.134 0.01 2 193 . 26 MET HG2 H 2.838 0.01 2 194 . 26 MET HG3 H 2.624 0.01 2 195 . 26 MET CA C 51.379 0.15 1 196 . 27 VAL H H 8.149 0.01 1 197 . 27 VAL HA H 3.546 0.01 1 198 . 27 VAL HB H 1.942 0.01 1 199 . 27 VAL HG1 H 0.981 0.01 2 200 . 27 VAL HG2 H 0.903 0.01 2 201 . 27 VAL CA C 63.763 0.15 1 202 . 28 ALA H H 8.470 0.01 1 203 . 28 ALA HA H 4.238 0.01 1 204 . 28 ALA HB H 1.491 0.01 1 205 . 28 ALA CA C 51.723 0.15 1 206 . 29 THR H H 7.425 0.01 1 207 . 29 THR HA H 4.824 0.01 1 208 . 29 THR HB H 4.310 0.01 1 209 . 29 THR HG2 H 1.199 0.01 1 210 . 29 THR CA C 55.557 0.15 1 211 . 30 PRO HA H 4.278 0.01 1 212 . 30 PRO HB2 H 2.043 0.01 1 213 . 30 PRO HB3 H 2.043 0.01 1 214 . 30 PRO HG2 H 1.748 0.01 1 215 . 30 PRO HG3 H 1.748 0.01 1 216 . 30 PRO HD2 H 3.580 0.01 1 217 . 30 PRO HD3 H 3.580 0.01 1 218 . 30 PRO CA C 62.313 0.15 1 219 . 31 LYS H H 8.306 0.01 1 220 . 31 LYS HA H 4.110 0.01 1 221 . 31 LYS HB2 H 1.960 0.01 2 222 . 31 LYS HB3 H 1.823 0.01 2 223 . 31 LYS HG2 H 1.638 0.01 1 224 . 31 LYS HG3 H 1.638 0.01 1 225 . 31 LYS HD2 H 1.429 0.01 2 226 . 31 LYS HD3 H 1.335 0.01 2 227 . 31 LYS CA C 55.167 0.15 1 228 . 32 VAL H H 7.565 0.01 1 229 . 32 VAL HA H 4.638 0.01 1 230 . 32 VAL HB H 2.162 0.01 1 231 . 32 VAL HG1 H 0.978 0.01 2 232 . 32 VAL HG2 H 0.920 0.01 2 233 . 32 VAL CA C 56.863 0.15 1 234 . 33 PRO HA H 4.331 0.01 1 235 . 33 PRO HB2 H 2.037 0.01 2 236 . 33 PRO HB3 H 1.795 0.01 2 237 . 33 PRO HG2 H 1.673 0.01 1 238 . 33 PRO HG3 H 1.673 0.01 1 239 . 33 PRO HD2 H 3.934 0.01 2 240 . 33 PRO HD3 H 3.836 0.01 2 241 . 33 PRO CA C 60.743 0.15 1 242 . 34 VAL H H 8.868 0.01 1 243 . 34 VAL HA H 4.309 0.01 1 244 . 34 VAL HB H 2.139 0.01 1 245 . 34 VAL HG1 H 1.050 0.01 2 246 . 34 VAL HG2 H 0.961 0.01 2 247 . 34 VAL CA C 59.892 0.15 1 248 . 35 LYS H H 7.389 0.01 1 249 . 35 LYS HA H 4.629 0.01 1 250 . 35 LYS HB2 H 1.716 0.01 2 251 . 35 LYS HB3 H 1.578 0.01 2 252 . 35 LYS HG2 H 1.853 0.01 1 253 . 35 LYS HG3 H 1.853 0.01 1 254 . 35 LYS HD2 H 2.048 0.01 1 255 . 35 LYS HD3 H 2.048 0.01 1 256 . 35 LYS HE2 H 3.090 0.01 1 257 . 35 LYS HE3 H 3.090 0.01 1 258 . 35 LYS CA C 53.902 0.15 1 259 . 36 ARG H H 8.364 0.01 1 260 . 36 ARG HA H 4.423 0.01 1 261 . 36 ARG HB2 H 1.625 0.01 2 262 . 36 ARG HB3 H 1.511 0.01 2 263 . 36 ARG HG2 H 1.054 0.01 1 264 . 36 ARG HG3 H 1.054 0.01 1 265 . 36 ARG HD2 H 3.142 0.01 2 266 . 36 ARG HD3 H 2.884 0.01 2 267 . 36 ARG HE H 8.416 0.01 1 268 . 36 ARG CA C 53.410 0.15 1 269 . 37 GLY H H 6.466 0.01 1 270 . 37 GLY HA2 H 4.364 0.01 2 271 . 37 GLY HA3 H 3.808 0.01 2 272 . 37 GLY CA C 44.044 0.15 1 273 . 38 CYS H H 9.260 0.01 1 274 . 38 CYS HA H 5.987 0.01 1 275 . 38 CYS HB2 H 3.578 0.01 2 276 . 38 CYS HB3 H 2.910 0.01 2 277 . 38 CYS CA C 53.763 0.15 1 278 . 39 ILE H H 9.937 0.01 1 279 . 39 ILE HA H 4.458 0.01 1 280 . 39 ILE HB H 1.734 0.01 1 281 . 39 ILE HG12 H 1.371 0.01 1 282 . 39 ILE HG13 H 1.371 0.01 1 283 . 39 ILE HG2 H 0.580 0.01 1 284 . 39 ILE HD1 H 0.451 0.01 1 285 . 39 ILE CA C 53.763 0.15 1 286 . 40 ASP H H 8.744 0.01 1 287 . 40 ASP HA H 4.897 0.01 1 288 . 40 ASP HB2 H 2.793 0.01 1 289 . 40 ASP HB3 H 2.793 0.01 1 290 . 40 ASP CA C 52.253 0.15 1 291 . 41 VAL H H 7.737 0.01 1 292 . 41 VAL HA H 4.018 0.01 1 293 . 41 VAL HB H 1.732 0.01 1 294 . 41 VAL HG1 H 0.765 0.01 1 295 . 41 VAL HG2 H 0.765 0.01 1 296 . 41 VAL CA C 58.018 0.15 1 297 . 42 CYS H H 8.912 0.01 1 298 . 42 CYS HA H 4.466 0.01 1 299 . 42 CYS HB2 H 3.090 0.01 2 300 . 42 CYS HB3 H 2.764 0.01 2 301 . 42 CYS CA C 52.513 0.15 1 302 . 43 PRO HA H 4.059 0.01 1 303 . 43 PRO HB2 H 1.751 0.01 2 304 . 43 PRO HB3 H 0.370 0.01 2 305 . 43 PRO HG2 H 1.247 0.01 2 306 . 43 PRO HG3 H 0.561 0.01 2 307 . 43 PRO HD2 H 3.931 0.01 2 308 . 43 PRO HD3 H 2.493 0.01 2 309 . 43 PRO CA C 59.698 0.15 1 310 . 44 LYS H H 8.029 0.01 1 311 . 44 LYS HA H 4.201 0.01 1 312 . 44 LYS HB2 H 1.727 0.01 1 313 . 44 LYS HB3 H 1.727 0.01 1 314 . 44 LYS HG2 H 1.565 0.01 1 315 . 44 LYS HG3 H 1.565 0.01 1 316 . 44 LYS HD2 H 1.834 0.01 1 317 . 44 LYS HD3 H 1.834 0.01 1 318 . 44 LYS HE2 H 3.042 0.01 1 319 . 44 LYS HE3 H 3.042 0.01 1 320 . 44 LYS CA C 54.034 0.15 1 321 . 45 SER H H 8.582 0.01 1 322 . 45 SER HA H 4.775 0.01 1 323 . 45 SER HB2 H 4.410 0.01 2 324 . 45 SER HB3 H 4.032 0.01 2 325 . 45 SER CA C 57.682 0.15 1 326 . 46 SER H H 9.436 0.01 1 327 . 46 SER HA H 5.004 0.01 1 328 . 46 SER HB2 H 4.472 0.01 2 329 . 46 SER HB3 H 3.974 0.01 2 330 . 46 SER CA C 53.928 0.15 1 331 . 47 LEU H H 8.269 0.01 1 332 . 47 LEU HA H 4.232 0.01 1 333 . 47 LEU HB2 H 1.763 0.01 1 334 . 47 LEU HB3 H 1.763 0.01 1 335 . 47 LEU HG H 1.639 0.01 1 336 . 47 LEU HD1 H 0.948 0.01 1 337 . 47 LEU HD2 H 0.948 0.01 1 338 . 47 LEU CA C 55.029 0.15 1 339 . 48 LEU H H 8.084 0.01 1 340 . 48 LEU HA H 4.545 0.01 1 341 . 48 LEU HB2 H 1.748 0.01 1 342 . 48 LEU HB3 H 1.748 0.01 1 343 . 48 LEU HG H 1.657 0.01 1 344 . 48 LEU HD1 H 0.947 0.01 2 345 . 48 LEU HD2 H 0.878 0.01 2 346 . 48 LEU CA C 53.483 0.15 1 347 . 49 VAL H H 7.538 0.01 1 348 . 49 VAL HA H 4.810 0.01 1 349 . 49 VAL HB H 1.900 0.01 1 350 . 49 VAL HG1 H 0.882 0.01 2 351 . 49 VAL HG2 H 0.763 0.01 2 352 . 49 VAL CA C 58.462 0.15 1 353 . 50 LYS H H 8.729 0.01 1 354 . 50 LYS HA H 4.813 0.01 1 355 . 50 LYS HB2 H 1.349 0.01 1 356 . 50 LYS HB3 H 1.349 0.01 1 357 . 50 LYS HG2 H 1.225 0.01 2 358 . 50 LYS HG3 H 1.148 0.01 2 359 . 50 LYS HD2 H 1.664 0.01 1 360 . 50 LYS HD3 H 1.664 0.01 1 361 . 50 LYS HE2 H 2.923 0.01 2 362 . 50 LYS HE3 H 2.842 0.01 2 363 . 50 LYS CA C 51.534 0.15 1 364 . 51 TYR H H 8.324 0.01 1 365 . 51 TYR HA H 5.293 0.01 1 366 . 51 TYR HB2 H 2.831 0.01 2 367 . 51 TYR HB3 H 2.635 0.01 2 368 . 51 TYR HD1 H 6.733 0.01 1 369 . 51 TYR HD2 H 6.733 0.01 1 370 . 51 TYR HE1 H 6.465 0.01 1 371 . 51 TYR HE2 H 6.465 0.01 1 372 . 51 TYR CA C 54.788 0.15 1 373 . 52 VAL H H 8.953 0.01 1 374 . 52 VAL HA H 4.556 0.01 1 375 . 52 VAL HB H 2.092 0.01 1 376 . 52 VAL HG1 H 1.149 0.01 2 377 . 52 VAL HG2 H 1.069 0.01 2 378 . 52 VAL CA C 59.688 0.15 1 379 . 53 CYS H H 9.471 0.01 1 380 . 53 CYS HA H 5.912 0.01 1 381 . 53 CYS HB2 H 3.803 0.01 2 382 . 53 CYS HB3 H 3.078 0.01 2 383 . 53 CYS CA C 52.609 0.15 1 384 . 54 CYS H H 9.166 0.01 1 385 . 54 CYS HA H 5.117 0.01 1 386 . 54 CYS HB2 H 3.650 0.01 2 387 . 54 CYS HB3 H 3.440 0.01 2 388 . 54 CYS CA C 52.872 0.15 1 389 . 55 ASN H H 8.595 0.01 1 390 . 55 ASN HA H 5.167 0.01 1 391 . 55 ASN HB2 H 3.402 0.01 2 392 . 55 ASN HB3 H 2.656 0.01 2 393 . 55 ASN HD21 H 6.740 0.01 2 394 . 55 ASN HD22 H 7.542 0.01 2 395 . 55 ASN CA C 50.689 0.15 1 396 . 56 THR H H 7.584 0.01 1 397 . 56 THR HA H 4.706 0.01 1 398 . 56 THR HG2 H 1.204 0.01 1 399 . 56 THR CA C 57.714 0.15 1 400 . 57 ASP H H 8.228 0.01 1 401 . 57 ASP HA H 4.856 0.01 1 402 . 57 ASP HB2 H 2.500 0.01 2 403 . 57 ASP HB3 H 2.274 0.01 2 404 . 57 ASP CA C 51.632 0.15 1 405 . 58 ARG H H 9.666 0.01 1 406 . 58 ARG HA H 3.407 0.01 1 407 . 58 ARG HB2 H 1.781 0.01 2 408 . 58 ARG HB3 H 1.372 0.01 2 409 . 58 ARG HG2 H 0.756 0.01 1 410 . 58 ARG HG3 H 0.756 0.01 1 411 . 58 ARG HD2 H 2.207 0.01 1 412 . 58 ARG HD3 H 2.207 0.01 1 413 . 58 ARG CA C 55.729 0.15 1 414 . 59 CYS H H 7.572 0.01 1 415 . 59 CYS HA H 4.473 0.01 1 416 . 59 CYS HB2 H 3.642 0.01 2 417 . 59 CYS HB3 H 3.363 0.01 2 418 . 59 CYS CA C 54.011 0.15 1 419 . 60 ASN H H 9.136 0.01 1 420 . 60 ASN HA H 4.387 0.01 1 421 . 60 ASN HB2 H 2.732 0.01 2 422 . 60 ASN HB3 H 2.357 0.01 2 423 . 60 ASN HD21 H 7.485 0.01 2 424 . 60 ASN HD22 H 7.642 0.01 2 425 . 60 ASN CA C 52.342 0.15 1 stop_ save_