data_5961 ####################### # Entry information # ####################### save_entry_information _Saveframe_category entry_information _Entry_title ; Binding site structure of one LRP/RAP complex - implications for a common ligand/receptor binding motif ; _BMRB_accession_number 5961 _BMRB_flat_file_name bmr5961.str _Entry_type original _Submission_date 2003-09-30 _Accession_date 2003-10-01 _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 Jensen Gitte A. . 2 Andersen Olav M. . 3 Bonvin Alexandre M.J.J. . 4 Bjerrum-Bohr Ida . . 5 Etzeroth Michael . . 6 Thoegersen Hans C. . 7 Poulsen Flemming M. . 8 Kragelund Birthe B. . stop_ loop_ _Saveframe_category_type _Saveframe_category_type_count assigned_chemical_shifts 1 stop_ loop_ _Data_type _Data_type_count "1H chemical shifts" 392 "15N chemical shifts" 80 stop_ loop_ _Revision_date _Revision_keyword _Revision_author _Revision_detail 2007-03-22 original BMRB . stop_ _Original_release_date 2003-10-01 save_ ############################# # Citation for this entry # ############################# save_entry_citation _Saveframe_category entry_citation _Citation_full . _Citation_title ; Binding site structure of one LRP-RAP complex: implications for a common ligand-receptor binding motif ; _Citation_status published _Citation_type journal _CAS_abstract_code . _MEDLINE_UI_code . _PubMed_ID 16938309 loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Jensen Gitte A. . 2 Andersen Olav M. . 3 Bonvin Alexandre M.J.J. . 4 Bjerrum-Bohr Ida . . 5 Etzerodt Michael . . 6 Thoegersen Hans C. . 7 O'Shea C. . . 8 Poulsen Flemming M. . 9 Kragelund Birthe B. . stop_ _Journal_abbreviation 'J. Mol. Biol.' _Journal_volume 362 _Journal_issue 4 _Journal_CSD . _Book_chapter_title . _Book_volume . _Book_series . _Book_ISBN . _Conference_state_province . _Conference_abstract_number . _Page_first 700 _Page_last 716 _Year 2006 _Details . loop_ _Keyword CR56 HADDOCK NMR RAP receptor 'recognition helix' stop_ save_ ####################################### # Cited references within the entry # ####################################### save_reference_1 _Saveframe_category citation _Citation_full ; Andersen OM, Christensen LL, Christensen PA, Sorensen ES, Jacobsen C, Moestrup SK, Etzerodt M, Thogersen HC. Identification of the minimal functional unit in the low density lipoprotein receptor-related protein for binding the receptor-associated protein (RAP). A conserved acidic residue in the complement-type repeats is important for recognition of RAP. J Biol Chem. 2000 Jul 14;275(28):21017-24. ; _Citation_title ; Identification of the minimal functional unit in the low density lipoprotein receptor-related protein for binding the receptor-associated protein (RAP). A conserved acidic residue in the complement-type repeats is important for recognition of RAP. ; _Citation_status published _Citation_type journal _CAS_abstract_code . _MEDLINE_UI_code . _PubMed_ID 10747921 loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Andersen O.M. M. . 2 Christensen L.L. L. . 3 Christensen P.A. A. . 4 Sorensen E.S. S. . 5 Jacobsen C. . . 6 Moestrup S.K. K. . 7 Etzerodt M. . . 8 Thogersen H.C. C. . stop_ _Journal_abbreviation 'J. Biol. Chem.' _Journal_name_full 'The Journal of biological chemistry' _Journal_volume 275 _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 21017 _Page_last 21024 _Year 2000 _Details ; The low density lipoprotein receptor-related protein (LRP), a member of the low density lipoprotein receptor family, mediates the internalization of a diverse set of ligands. The ligand binding sites are located in different regions of clusters consisting of approximately 40 residues, cysteine-rich complement-type repeats (CRs). The 39-40-kDa receptor-associated protein, a folding chaperone/escort protein required for efficient transport of functional LRP to the cell surface, is an antagonist of all identified ligands. To analyze the multisite inhibition by RAP in ligand binding of LRP, we have used an Escherichia coli expression system to produce fragments of the entire second ligand binding cluster of LRP (CR3-10). By ligand affinity chromatography and surface plasmon resonance analysis, we show that RAP binds to all two-repeat modules except CR910. CR10 differs from other repeats in cluster II by not containing a surface-exposed conserved acidic residue between Cys(IV) and Cys(V). By site-directed mutagenesis and ligand competition analysis, we provide evidence for a crucial importance of this conserved residue for RAP binding. We provide experimental evidence showing that two adjacent complement-type repeats, both containing a conserved acidic residue, represent a minimal unit required for efficient binding to RAP. ; save_ save_reference_2 _Saveframe_category citation _Citation_full ; The solution structure of the N-terminal domain of alpha2-macroglobulin receptor-associated protein. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7521-5. ; _Citation_title ; The solution structure of the N-terminal domain of alpha2-macroglobulin receptor-associated protein. ; _Citation_status published _Citation_type journal _CAS_abstract_code . _MEDLINE_UI_code . _PubMed_ID 9207124 loop_ _Author_ordinal _Author_family_name _Author_given_name _Author_middle_initials _Author_family_title 1 Nielsen P.R. R. . 2 Ellgaard L. . . 3 Etzerodt M. . . 4 Thogersen H.C. C. . 5 Poulsen F.M. M. . stop_ _Journal_abbreviation 'Proc. Natl. Acad. Sci. U.S.A.' _Journal_name_full 'Proceedings of the National Academy of Sciences of the United States of America' _Journal_volume 94 _Journal_issue 14 _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 7521 _Page_last 7525 _Year 1997 _Details ; The three-dimensional structure of the N-terminal domain (residues 18-112) of alpha2-macroglobulin receptor-associated protein (RAP) has been determined by NMR spectroscopy. The structure consists of three helices composed of residues 23-34, 39-65, and 73-88. The three helices are arranged in an up-down-up antiparallel topology. The C-terminal 20 residues were shown not to be in a well defined conformation. A structural model for the binding of RAP to the family of low-density lipoprotein receptors is proposed. It defines a role in binding for both the unordered C terminus and the structural scaffold of the core structure. Pathogenic epitopes for the rat disease Heymann nephritis, an experimental model of human membranous glomerulonephritis, have been identified in RAP and in the large endocytic receptor gp330/megalin. Here we provide the three-dimensional structure of the pathogenic epitope in RAP. The amino acid residues known to form the epitope are in a helix-loop-helix conformation, and from the structure it is possible to rationalize the published results obtained from studies of fragments of the N-terminal domain. ; save_ ################################## # Molecular system description # ################################## save_system_CR56 _Saveframe_category molecular_system _Mol_system_name 'complement type repeats 5 and 6 from LRP' _Abbreviation_common CR56 _Enzyme_commission_number . loop_ _Mol_system_component_name _Mol_label CR56 $CR56 'CALCIUM (II) ION, 1' $CA 'CALCIUM (II) ION, 2' $CA stop_ _System_molecular_weight . _System_physical_state native _System_oligomer_state monomer _System_paramagnetic no _System_thiol_state 'all disulfide bound' loop_ _Biological_function 'LRP receptor unit' 'ligand binding repeat' 'minimal binding unit' stop_ _Database_query_date . _Details . save_ ######################## # Monomeric polymers # ######################## save_CR56 _Saveframe_category monomeric_polymer _Mol_type polymer _Mol_polymer_class protein _Name_common 'complement type repeats 5 and 6' _Abbreviation_common CR56 _Molecular_mass 8938.61 _Mol_thiol_state 'all disulfide bound' _Details 'CR56 binds two Ca2+ ions.' ############################## # Polymer residue sequence # ############################## _Residue_count 82 _Mol_residue_sequence ; SARTCPPNQFSCASGRCIPI SWTCDLDDDCGDRSDESASC AYPTCFPLTQFTCNNGRCIN INWRCDNDNDCGDNSDEAGC SH ; loop_ _Residue_seq_code _Residue_author_seq_code _Residue_label 1 932 SER 2 933 ALA 3 934 ARG 4 935 THR 5 936 CYS 6 937 PRO 7 938 PRO 8 939 ASN 9 940 GLN 10 941 PHE 11 942 SER 12 943 CYS 13 944 ALA 14 945 SER 15 946 GLY 16 947 ARG 17 948 CYS 18 949 ILE 19 950 PRO 20 951 ILE 21 952 SER 22 953 TRP 23 954 THR 24 955 CYS 25 956 ASP 26 957 LEU 27 958 ASP 28 959 ASP 29 960 ASP 30 961 CYS 31 962 GLY 32 963 ASP 33 964 ARG 34 965 SER 35 966 ASP 36 967 GLU 37 968 SER 38 969 ALA 39 970 SER 40 971 CYS 41 972 ALA 42 973 TYR 43 974 PRO 44 975 THR 45 976 CYS 46 977 PHE 47 978 PRO 48 979 LEU 49 980 THR 50 981 GLN 51 982 PHE 52 983 THR 53 984 CYS 54 985 ASN 55 986 ASN 56 987 GLY 57 988 ARG 58 989 CYS 59 990 ILE 60 991 ASN 61 992 ILE 62 993 ASN 63 994 TRP 64 995 ARG 65 996 CYS 66 997 ASP 67 998 ASN 68 999 ASP 69 1000 ASN 70 1001 ASP 71 1002 CYS 72 1003 GLY 73 1004 ASP 74 1005 ASN 75 1006 SER 76 1007 ASP 77 1008 GLU 78 1009 ALA 79 1010 GLY 80 1011 CYS 81 1012 SER 82 1013 HIS 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 PDB 2FYJ 'Nmr Solution Structure Of Calcium-Loaded Lrp Double Module' 100.00 82 100.00 100.00 3.47e-39 PDB 2FYL 'Haddock Model Of The Complex Between Double Module Of Lrp, Cr56, And First Domain Of Receptor Associated Protein, Rap- D1' 100.00 82 100.00 100.00 3.47e-39 stop_ save_ ############# # Ligands # ############# save_CA _Saveframe_category ligand _Mol_type non-polymer _Name_common "CA (CALCIUM ION)" _BMRB_code . _PDB_code CA _Molecular_mass 40.078 _Mol_charge 2 _Mol_paramagnetic . _Mol_aromatic no _Details ; Information obtained from PDB's Chemical Component Dictionary at http://wwpdb-remediation.rutgers.edu/downloads.html Downloaded on Thu Jul 21 10:35:28 2011 ; loop_ _Atom_name _PDB_atom_name _Atom_type _Atom_chirality _Atom_charge _Atom_oxidation_number _Atom_unpaired_electrons CA CA CA . 2 . ? stop_ _Mol_thiol_state . _Sequence_homology_query_date . save_ #################### # Natural source # #################### save_natural_source _Saveframe_category natural_source loop_ _Mol_label _Organism_name_common _NCBI_taxonomy_ID _Superkingdom _Kingdom _Genus _Species $CR56 Human 9606 Eukaryota Metazoa Homo sapiens 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 $CR56 'recombinant technology' 'Escherichis coli' Escherichis coli BL21(DE3) pT7 stop_ save_ ##################################### # Sample contents and methodology # ##################################### ######################## # Sample description # ######################## save_sample_1 _Saveframe_category sample _Sample_type solution _Details . loop_ _Mol_label _Concentration_value _Concentration_value_units _Isotopic_labeling $CR56 0.5 mM . CaCl2 10 mM . MgCl2 1 mM . NaCl 100 mM . stop_ save_ save_sample_2 _Saveframe_category sample _Sample_type solution _Details . loop_ _Mol_label _Concentration_value _Concentration_value_units _Isotopic_labeling $CR56 0.5 mM '[U-99% 15N]' CaCl2 10 mM . MgCl2 1 mM . NaCl 100 mM . stop_ save_ ############################ # Computer software used # ############################ save_PRONTO _Saveframe_category software _Name PRONTO _Version 20020517 loop_ _Task 'assignment tool' stop_ _Details ; 'Carlsberg A/S' Gamle Carlsberg Vej 10, DK-2500 Valby mk@crc.dk ; save_ ######################### # Experimental detail # ######################### ################################## # NMR Spectrometer definitions # ################################## save_NMR_spectrometer_1 _Saveframe_category NMR_spectrometer _Manufacturer Varian _Model UNITY _Field_strength 750 _Details . save_ save_NMR_spectrometer_2 _Saveframe_category NMR_spectrometer _Manufacturer Varian _Model UNITY _Field_strength 800 _Details . save_ ############################# # NMR applied experiments # ############################# save_DQF-COSY_1 _Saveframe_category NMR_applied_experiment _Experiment_name DQF-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_15N-HSQC_4 _Saveframe_category NMR_applied_experiment _Experiment_name 15N-HSQC _Sample_label . save_ save_15N-NOESY-HSQC_5 _Saveframe_category NMR_applied_experiment _Experiment_name 15N-NOESY-HSQC _Sample_label . save_ save_15N-TOCSY-HSQC_6 _Saveframe_category NMR_applied_experiment _Experiment_name 15N-TOCSY-HSQC _Sample_label . save_ ####################### # Sample conditions # ####################### save_conditions _Saveframe_category sample_conditions _Details . loop_ _Variable_type _Variable_value _Variable_value_error _Variable_value_units pH 7.0 0.1 pH temperature 298 1 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 H 1 'methyl protons' ppm 0.0 internal direct . . . 1.0 DSS N 15 'methyl protons' ppm 0.0 external indirect . . . 0.10132905 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_chemical_shift_1 _Saveframe_category assigned_chemical_shifts _Details . loop_ _Experiment_label DQF-COSY NOESY TOCSY 15N-HSQC 15N-NOESY-HSQC 15N-TOCSY-HSQC stop_ _Sample_conditions_label $conditions _Chem_shift_reference_set_label $chemical_shift_reference _Mol_system_component_name CR56 _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 SER H H 7.80 . 1 2 . 1 SER HA H 4.44 . 1 3 . 1 SER HB2 H 2.94 . 2 4 . 1 SER HB3 H 2.79 . 2 5 . 1 SER N N 118.41 . 1 6 . 2 ALA HB H 1.34 . 1 7 . 2 ALA HA H 4.28 . 1 8 . 3 ARG H H 8.39 . 1 9 . 3 ARG HA H 4.39 . 1 10 . 3 ARG HB3 H 1.82 . 2 11 . 3 ARG HB2 H 1.71 . 2 12 . 3 ARG HG2 H 1.56 . 2 13 . 3 ARG HD2 H 3.13 . 2 14 . 3 ARG N N 120.65 . 1 15 . 4 THR H H 8.14 . 1 16 . 4 THR HA H 4.28 . 1 17 . 4 THR HG2 H 1.13 . 1 18 . 4 THR HB H 4.10 . 1 19 . 4 THR N N 115.81 . 1 20 . 5 CYS H H 8.38 . 1 21 . 5 CYS HA H 5.06 . 1 22 . 5 CYS HB3 H 2.42 . 2 23 . 5 CYS HB2 H 2.84 . 2 24 . 5 CYS N N 122.35 . 1 25 . 6 PRO HG2 H 1.92 . 2 26 . 6 PRO HB3 H 1.67 . 2 27 . 6 PRO HB2 H 2.44 . 2 28 . 6 PRO HD3 H 3.41 . 2 29 . 6 PRO HD2 H 3.84 . 2 30 . 6 PRO HG3 H 1.86 . 2 31 . 7 PRO HD3 H 3.54 . 2 32 . 7 PRO HG3 H 1.97 . 2 33 . 7 PRO HB3 H 1.82 . 2 34 . 7 PRO HB2 H 2.30 . 2 35 . 7 PRO HA H 4.30 . 1 36 . 7 PRO HG2 H 2.02 . 2 37 . 7 PRO HD2 H 3.74 . 2 38 . 8 ASN HA H 4.42 . 1 39 . 8 ASN HB2 H 3.08 . 2 40 . 8 ASN HB3 H 2.89 . 2 41 . 8 ASN HD22 H 6.87 . 2 42 . 8 ASN HD21 H 7.53 . 2 43 . 8 ASN ND2 N 113.05 . 1 44 . 8 ASN H H 7.53 . 1 45 . 9 GLN HB3 H 1.77 . 2 46 . 9 GLN HB2 H 2.12 . 2 47 . 9 GLN H H 7.86 . 1 48 . 9 GLN HA H 4.79 . 1 49 . 9 GLN N N 118.12 . 1 50 . 9 GLN HE22 H 6.31 . 2 51 . 9 GLN HE21 H 7.04 . 2 52 . 9 GLN NE2 N 108.09 . 1 53 . 9 GLN HG3 H 1.85 . 2 54 . 9 GLN HG2 H 2.43 . 2 55 . 10 PHE H H 9.73 . 1 56 . 10 PHE N N 123.55 . 1 57 . 10 PHE HA H 4.57 . 1 58 . 10 PHE HB3 H 2.66 . 2 59 . 10 PHE HB2 H 2.73 . 2 60 . 10 PHE HE1 H 7.28 . 3 61 . 10 PHE HD1 H 7.04 . 3 62 . 10 PHE HZ H 7.32 . 1 63 . 11 SER H H 7.57 . 1 64 . 11 SER HA H 4.59 . 1 65 . 11 SER N N 120.78 . 1 66 . 11 SER HB3 H 3.45 . 2 67 . 11 SER HB2 H 3.52 . 2 68 . 12 CYS H H 8.70 . 1 69 . 12 CYS HA H 4.61 . 1 70 . 12 CYS N N 125.71 . 1 71 . 12 CYS HB3 H 3.10 . 2 72 . 12 CYS HB2 H 3.49 . 2 73 . 13 ALA H H 9.16 . 1 74 . 13 ALA HA H 4.05 . 1 75 . 13 ALA HB H 1.55 . 1 76 . 13 ALA N N 129.85 . 1 77 . 14 SER HB3 H 3.48 . 2 78 . 14 SER H H 7.98 . 1 79 . 14 SER HA H 4.21 . 1 80 . 14 SER N N 110.32 . 1 81 . 14 SER HB2 H 3.91 . 2 82 . 15 GLY H H 7.86 . 1 83 . 15 GLY HA2 H 4.41 . 2 84 . 15 GLY N N 110.80 . 1 85 . 15 GLY HA3 H 3.49 . 2 86 . 16 ARG H H 7.15 . 1 87 . 16 ARG HA H 4.16 . 1 88 . 16 ARG N N 120.87 . 1 89 . 16 ARG HB2 H 1.64 . 2 90 . 16 ARG HG2 H 1.71 . 2 91 . 16 ARG HB3 H 1.81 . 2 92 . 16 ARG HD2 H 3.22 . 2 93 . 17 CYS H H 8.52 . 1 94 . 17 CYS HB3 H 2.72 . 2 95 . 17 CYS HB2 H 3.15 . 2 96 . 17 CYS HA H 5.57 . 1 97 . 17 CYS N N 124.01 . 1 98 . 18 ILE HB H 1.86 . 1 99 . 18 ILE HG2 H 0.95 . 1 100 . 18 ILE HG13 H 1.33 . 2 101 . 18 ILE HG12 H 1.56 . 2 102 . 18 ILE HD1 H 0.98 . 1 103 . 18 ILE H H 8.94 . 1 104 . 18 ILE N N 116.83 . 1 105 . 18 ILE HA H 4.60 . 1 106 . 19 PRO HB2 H 1.99 . 2 107 . 19 PRO HB3 H 0.74 . 2 108 . 19 PRO HA H 4.11 . 1 109 . 20 ILE HA H 3.84 . 1 110 . 20 ILE HG13 H 1.24 . 2 111 . 20 ILE HG12 H 1.39 . 2 112 . 20 ILE HG2 H 0.89 . 1 113 . 20 ILE H H 7.98 . 1 114 . 20 ILE N N 123.90 . 1 115 . 20 ILE HB H 1.56 . 1 116 . 20 ILE HD1 H 0.91 . 1 117 . 21 SER HB2 H 4.17 . 2 118 . 21 SER HB3 H 3.92 . 2 119 . 21 SER HA H 4.36 . 1 120 . 22 TRP HE1 H 10.06 . 1 121 . 22 TRP HD1 H 6.96 . 1 122 . 22 TRP HZ2 H 7.47 . 1 123 . 22 TRP HH2 H 7.27 . 1 124 . 22 TRP H H 7.93 . 1 125 . 22 TRP HA H 5.16 . 1 126 . 22 TRP HB2 H 3.67 . 2 127 . 22 TRP N N 120.60 . 1 128 . 22 TRP NE1 N 127.64 . 1 129 . 22 TRP HB3 H 3.23 . 2 130 . 22 TRP HE3 H 7.35 . 1 131 . 22 TRP HZ3 H 7.23 . 1 132 . 23 THR HG2 H 0.51 . 1 133 . 23 THR HB H 4.00 . 1 134 . 23 THR H H 8.26 . 1 135 . 23 THR N N 116.56 . 1 136 . 23 THR HA H 4.41 . 1 137 . 24 CYS HB2 H 3.14 . 2 138 . 24 CYS HB3 H 2.97 . 2 139 . 24 CYS H H 8.81 . 1 140 . 24 CYS HA H 4.90 . 1 141 . 24 CYS N N 117.78 . 1 142 . 25 ASP HB2 H 3.07 . 2 143 . 25 ASP HB3 H 2.38 . 2 144 . 25 ASP H H 9.99 . 1 145 . 25 ASP HA H 4.87 . 1 146 . 25 ASP N N 122.38 . 1 147 . 26 LEU H H 9.07 . 1 148 . 26 LEU HA H 3.48 . 1 149 . 26 LEU HB2 H 2.30 . 2 150 . 26 LEU HB3 H 1.34 . 2 151 . 26 LEU HG H 1.18 . 1 152 . 26 LEU HD1 H 0.31 . 2 153 . 26 LEU HD2 H 0.62 . 2 154 . 26 LEU N N 114.39 . 1 155 . 27 ASP H H 7.62 . 1 156 . 27 ASP HA H 4.84 . 1 157 . 27 ASP HB2 H 2.59 . 2 158 . 27 ASP HB3 H 2.45 . 2 159 . 27 ASP N N 118.76 . 1 160 . 29 ASP H H 10.19 . 1 161 . 29 ASP HA H 4.83 . 1 162 . 29 ASP N N 127.52 . 1 163 . 29 ASP HB3 H 2.82 . 2 164 . 29 ASP HB2 H 3.02 . 2 165 . 30 CYS H H 8.56 . 1 166 . 30 CYS HB2 H 3.51 . 2 167 . 30 CYS N N 118.21 . 1 168 . 30 CYS HA H 4.77 . 1 169 . 30 CYS HB3 H 3.17 . 2 170 . 31 GLY H H 9.44 . 1 171 . 31 GLY HA3 H 3.66 . 2 172 . 31 GLY N N 114.60 . 1 173 . 31 GLY HA2 H 4.42 . 2 174 . 32 ASP H H 7.30 . 1 175 . 32 ASP N N 118.25 . 1 176 . 32 ASP HB2 H 3.70 . 2 177 . 32 ASP HB3 H 3.51 . 2 178 . 32 ASP HA H 4.74 . 1 179 . 33 ARG H H 9.34 . 1 180 . 33 ARG HA H 3.70 . 1 181 . 33 ARG N N 115.49 . 1 182 . 33 ARG HB2 H 1.94 . 2 183 . 33 ARG HB3 H 2.14 . 2 184 . 33 ARG HG2 H 1.30 . 2 185 . 33 ARG HG3 H 1.52 . 2 186 . 34 SER H H 9.16 . 1 187 . 34 SER HA H 4.21 . 1 188 . 34 SER N N 116.68 . 1 189 . 34 SER HB2 H 4.41 . 2 190 . 34 SER HB3 H 4.09 . 2 191 . 35 ASP HB3 H 2.51 . 2 192 . 35 ASP HB2 H 2.95 . 2 193 . 35 ASP H H 10.38 . 1 194 . 35 ASP HA H 4.11 . 1 195 . 35 ASP N N 115.85 . 1 196 . 36 GLU H H 7.65 . 1 197 . 36 GLU HB3 H 1.50 . 2 198 . 36 GLU N N 121.48 . 1 199 . 36 GLU HA H 4.89 . 1 200 . 36 GLU HG3 H 2.35 . 2 201 . 37 SER H H 7.51 . 1 202 . 37 SER HA H 4.63 . 1 203 . 37 SER N N 116.22 . 1 204 . 37 SER HB3 H 3.93 . 2 205 . 37 SER HB2 H 4.23 . 2 206 . 38 ALA HA H 4.29 . 1 207 . 38 ALA HB H 1.46 . 1 208 . 38 ALA H H 8.46 . 1 209 . 39 SER H H 8.01 . 1 210 . 39 SER HA H 4.22 . 1 211 . 39 SER N N 111.96 . 1 212 . 39 SER HB3 H 3.84 . 2 213 . 40 CYS H H 7.81 . 1 214 . 40 CYS HA H 4.31 . 1 215 . 40 CYS HB2 H 2.56 . 2 216 . 40 CYS HB3 H 2.16 . 2 217 . 40 CYS N N 120.52 . 1 218 . 41 ALA H H 8.17 . 1 219 . 41 ALA HA H 4.38 . 1 220 . 41 ALA HB H 1.22 . 1 221 . 41 ALA N N 126.02 . 1 222 . 42 TYR H H 7.96 . 1 223 . 42 TYR HB2 H 3.12 . 2 224 . 42 TYR HB3 H 2.65 . 2 225 . 42 TYR HD1 H 7.06 . 3 226 . 42 TYR HE1 H 6.66 . 3 227 . 42 TYR N N 121.81 . 1 228 . 42 TYR HA H 4.80 . 1 229 . 43 PRO HB2 H 2.27 . 2 230 . 43 PRO HG3 H 2.03 . 2 231 . 43 PRO HB3 H 1.91 . 2 232 . 43 PRO HD3 H 3.71 . 2 233 . 43 PRO HD2 H 3.87 . 2 234 . 43 PRO HA H 4.43 . 1 235 . 43 PRO HG2 H 2.56 . 2 236 . 44 THR H H 8.01 . 1 237 . 44 THR HA H 4.21 . 1 238 . 44 THR HG2 H 1.16 . 1 239 . 44 THR HB H 4.00 . 1 240 . 44 THR N N 114.63 . 1 241 . 45 CYS HB2 H 2.77 . 2 242 . 45 CYS HB3 H 2.43 . 2 243 . 45 CYS H H 8.36 . 1 244 . 45 CYS N N 122.19 . 1 245 . 45 CYS HA H 4.65 . 1 246 . 46 PHE HB2 H 3.18 . 2 247 . 46 PHE HB3 H 2.80 . 2 248 . 46 PHE HA H 4.82 . 1 249 . 46 PHE H H 8.91 . 1 250 . 46 PHE N N 126.37 . 1 251 . 46 PHE HD1 H 7.28 . 3 252 . 46 PHE HE1 H 7.34 . 3 253 . 47 PRO HD3 H 3.68 . 2 254 . 47 PRO HD2 H 4.01 . 2 255 . 47 PRO HG2 H 1.98 . 2 256 . 47 PRO HA H 4.41 . 1 257 . 47 PRO HB3 H 2.34 . 2 258 . 47 PRO HG3 H 1.95 . 2 259 . 47 PRO HB2 H 1.88 . 2 260 . 48 LEU HB3 H 1.50 . 2 261 . 48 LEU HD1 H 0.86 . 2 262 . 48 LEU HG H 1.55 . 1 263 . 48 LEU HB2 H 1.87 . 2 264 . 48 LEU HD2 H 0.90 . 2 265 . 48 LEU HA H 4.18 . 1 266 . 48 LEU H H 7.94 . 1 267 . 48 LEU N N 114.54 . 1 268 . 49 THR HA H 4.42 . 1 269 . 49 THR HB H 4.35 . 1 270 . 49 THR HG2 H 1.10 . 1 271 . 49 THR H H 7.52 . 1 272 . 49 THR N N 104.56 . 1 273 . 50 GLN H H 8.13 . 1 274 . 50 GLN HA H 5.26 . 1 275 . 50 GLN HB2 H 2.31 . 2 276 . 50 GLN HB3 H 1.61 . 2 277 . 50 GLN HG2 H 2.53 . 2 278 . 50 GLN HG3 H 1.98 . 2 279 . 50 GLN HE22 H 6.38 . 2 280 . 50 GLN HE21 H 7.45 . 2 281 . 50 GLN N N 121.16 . 1 282 . 50 GLN NE2 N 112.46 . 1 283 . 51 PHE HB2 H 2.88 . 2 284 . 51 PHE HB3 H 2.63 . 2 285 . 51 PHE H H 9.06 . 1 286 . 51 PHE N N 122.34 . 1 287 . 51 PHE HA H 4.64 . 1 288 . 51 PHE HE1 H 7.33 . 3 289 . 51 PHE HD1 H 7.10 . 3 290 . 51 PHE HZ H 7.25 . 1 291 . 52 THR H H 7.43 . 1 292 . 52 THR HA H 4.43 . 1 293 . 52 THR HG2 H 1.02 . 1 294 . 52 THR HB H 3.65 . 1 295 . 52 THR N N 123.59 . 1 296 . 53 CYS H H 8.82 . 1 297 . 53 CYS HB2 H 3.37 . 2 298 . 53 CYS HB3 H 2.96 . 2 299 . 53 CYS HA H 4.46 . 1 300 . 53 CYS N N 126.41 . 1 301 . 54 ASN HA H 4.33 . 1 302 . 54 ASN HB3 H 2.87 . 2 303 . 54 ASN HB2 H 3.08 . 2 304 . 54 ASN H H 9.31 . 1 305 . 54 ASN HD22 H 7.04 . 2 306 . 54 ASN N N 125.29 . 1 307 . 54 ASN HD21 H 7.77 . 2 308 . 54 ASN ND2 N 111.99 . 1 309 . 55 ASN H H 7.47 . 1 310 . 55 ASN HA H 4.41 . 1 311 . 55 ASN HB2 H 3.22 . 2 312 . 55 ASN HB3 H 2.75 . 2 313 . 55 ASN HD21 H 7.47 . 2 314 . 55 ASN N N 114.92 . 1 315 . 55 ASN ND2 N 105.52 . 1 316 . 55 ASN HD22 H 6.71 . 2 317 . 56 GLY H H 7.77 . 1 318 . 56 GLY HA2 H 4.13 . 2 319 . 56 GLY HA3 H 3.32 . 2 320 . 56 GLY N N 107.57 . 1 321 . 57 ARG HD2 H 3.28 . 2 322 . 57 ARG HG2 H 1.54 . 2 323 . 57 ARG HG3 H 1.59 . 2 324 . 57 ARG H H 7.52 . 1 325 . 57 ARG HA H 3.98 . 1 326 . 57 ARG HB3 H 1.86 . 2 327 . 57 ARG N N 120.19 . 1 328 . 57 ARG HB2 H 1.14 . 2 329 . 58 CYS H H 8.34 . 1 330 . 58 CYS HA H 5.49 . 1 331 . 58 CYS HB3 H 2.61 . 2 332 . 58 CYS N N 120.29 . 1 333 . 59 ILE HG13 H 1.32 . 2 334 . 59 ILE HG2 H 0.95 . 1 335 . 59 ILE HB H 2.11 . 1 336 . 59 ILE HD1 H 1.06 . 1 337 . 59 ILE HG12 H 1.53 . 2 338 . 59 ILE H H 8.57 . 1 339 . 59 ILE HA H 4.86 . 1 340 . 59 ILE N N 114.98 . 1 341 . 60 ASN HA H 4.09 . 1 342 . 60 ASN H H 6.85 . 1 343 . 60 ASN N N 121.45 . 1 344 . 60 ASN HB3 H 0.96 . 2 345 . 60 ASN HD22 H 6.93 . 2 346 . 60 ASN HD21 H 7.04 . 2 347 . 60 ASN ND2 N 112.90 . 1 348 . 60 ASN HB2 H 1.43 . 2 349 . 61 ILE HA H 3.87 . 1 350 . 61 ILE HB H 1.22 . 1 351 . 61 ILE HD1 H 0.89 . 1 352 . 61 ILE HG13 H 1.34 . 2 353 . 61 ILE H H 8.01 . 1 354 . 61 ILE N N 127.30 . 1 355 . 61 ILE HG2 H 0.81 . 1 356 . 62 ASN H H 8.60 . 1 357 . 62 ASN HA H 4.56 . 1 358 . 62 ASN HB3 H 2.47 . 2 359 . 62 ASN HB2 H 2.85 . 2 360 . 62 ASN N N 119.23 . 1 361 . 62 ASN HD22 H 6.96 . 2 362 . 62 ASN ND2 N 113.67 . 1 363 . 62 ASN HD21 H 7.60 . 2 364 . 63 TRP H H 8.08 . 1 365 . 63 TRP HA H 5.14 . 1 366 . 63 TRP HB3 H 3.26 . 2 367 . 63 TRP HB2 H 3.75 . 2 368 . 63 TRP HD1 H 6.75 . 1 369 . 63 TRP HE1 H 10.15 . 1 370 . 63 TRP N N 118.69 . 1 371 . 63 TRP NE1 N 128.47 . 1 372 . 63 TRP HZ2 H 7.54 . 1 373 . 63 TRP HH2 H 7.28 . 1 374 . 63 TRP HE3 H 7.40 . 1 375 . 63 TRP HZ3 H 7.31 . 1 376 . 64 ARG H H 7.59 . 1 377 . 64 ARG HA H 4.12 . 1 378 . 64 ARG HB3 H 1.99 . 2 379 . 64 ARG HG2 H 1.26 . 2 380 . 64 ARG HD3 H 2.87 . 2 381 . 64 ARG HB2 H 1.22 . 2 382 . 64 ARG N N 126.84 . 1 383 . 64 ARG HD2 H 2.19 . 2 384 . 64 ARG HG3 H 1.39 . 2 385 . 65 CYS H H 8.65 . 1 386 . 65 CYS HA H 4.98 . 1 387 . 65 CYS HB2 H 3.30 . 2 388 . 65 CYS HB3 H 3.02 . 2 389 . 65 CYS N N 123.17 . 1 390 . 66 ASP H H 9.66 . 1 391 . 66 ASP HB2 H 3.13 . 2 392 . 66 ASP HB3 H 2.94 . 2 393 . 66 ASP N N 122.28 . 1 394 . 66 ASP HA H 4.78 . 1 395 . 67 ASN H H 9.23 . 1 396 . 67 ASN HB3 H 2.94 . 2 397 . 67 ASN HB2 H 3.14 . 2 398 . 67 ASN HA H 4.08 . 1 399 . 67 ASN N N 114.13 . 1 400 . 67 ASN HD22 H 6.78 . 2 401 . 67 ASN ND2 N 113.04 . 1 402 . 67 ASN HD21 H 7.44 . 2 403 . 68 ASP H H 7.60 . 1 404 . 68 ASP HB3 H 2.45 . 2 405 . 68 ASP HB2 H 2.59 . 2 406 . 68 ASP N N 117.26 . 1 407 . 68 ASP HA H 4.86 . 1 408 . 69 ASN HD22 H 5.99 . 2 409 . 69 ASN HD21 H 7.70 . 2 410 . 69 ASN ND2 N 109.44 . 1 411 . 69 ASN HB3 H 2.91 . 2 412 . 69 ASN HB2 H 3.13 . 2 413 . 69 ASN H H 7.59 . 1 414 . 69 ASN N N 117.22 . 1 415 . 69 ASN HA H 4.82 . 1 416 . 70 ASP H H 10.27 . 1 417 . 70 ASP HA H 4.79 . 1 418 . 70 ASP N N 127.00 . 1 419 . 70 ASP HB3 H 2.84 . 2 420 . 70 ASP HB2 H 2.88 . 2 421 . 71 CYS H H 8.70 . 1 422 . 71 CYS HA H 4.47 . 1 423 . 71 CYS N N 117.47 . 1 424 . 71 CYS HB3 H 3.29 . 2 425 . 71 CYS HB2 H 3.34 . 2 426 . 72 GLY H H 8.11 . 1 427 . 72 GLY HA3 H 3.53 . 2 428 . 72 GLY N N 110.24 . 1 429 . 72 GLY HA2 H 4.66 . 2 430 . 73 ASP H H 6.90 . 1 431 . 73 ASP N N 118.20 . 1 432 . 73 ASP HA H 4.46 . 1 433 . 73 ASP HB3 H 2.61 . 2 434 . 73 ASP HB2 H 3.25 . 2 435 . 74 ASN H H 8.42 . 1 436 . 74 ASN HA H 4.46 . 1 437 . 74 ASN HB3 H 2.43 . 2 438 . 74 ASN HB2 H 3.15 . 2 439 . 74 ASN N N 116.22 . 1 440 . 74 ASN HD22 H 6.45 . 2 441 . 74 ASN ND2 N 107.98 . 1 442 . 74 ASN HD21 H 7.18 . 2 443 . 75 SER H H 9.22 . 1 444 . 75 SER N N 117.86 . 1 445 . 75 SER HB3 H 3.99 . 2 446 . 75 SER HA H 4.11 . 1 447 . 75 SER HB2 H 4.21 . 2 448 . 76 ASP H H 10.17 . 1 449 . 76 ASP HA H 3.96 . 1 450 . 76 ASP HB3 H 2.44 . 2 451 . 76 ASP HB2 H 3.07 . 2 452 . 76 ASP N N 116.18 . 1 453 . 77 GLU H H 7.52 . 1 454 . 77 GLU HA H 4.44 . 1 455 . 77 GLU N N 118.27 . 1 456 . 77 GLU HB3 H 1.49 . 2 457 . 77 GLU HG2 H 2.32 . 2 458 . 77 GLU HB2 H 1.87 . 2 459 . 77 GLU HG3 H 2.03 . 2 460 . 78 ALA H H 7.03 . 1 461 . 78 ALA HA H 4.42 . 1 462 . 78 ALA N N 124.56 . 1 463 . 78 ALA HB H 1.44 . 1 464 . 81 SER HA H 4.39 . 1 465 . 81 SER HB3 H 3.81 . 2 466 . 82 HIS H H 8.09 . 1 467 . 82 HIS HA H 4.45 . 1 468 . 82 HIS HB3 H 3.04 . 2 469 . 82 HIS HB2 H 3.22 . 2 470 . 82 HIS HD2 H 7.14 . 1 471 . 82 HIS HE1 H 8.37 . 1 472 . 82 HIS HD1 H 10.94 . 1 stop_ save_