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(-) Description

Title :  STRUCTURE OF BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH2-(2-(1H-IMIDAZOL-1-YL)PYRIMIDIN-4-YL)-N-(3-CYANOBENZYL)ETHAN-1-AMINE
 
Authors :  H. Li, T. L. Poulos
Date :  20 Oct 14  (Deposition) - 24 Dec 14  (Release) - 04 Mar 15  (Revision)
Method :  X-RAY DIFFRACTION
Resolution :  2.00
Chains :  Asym./Biol. Unit :  A,B
Keywords :  Oxidoreductase, Nitric Oxide Synthase, Inhibitor Complex (Keyword Search: [Gene Ontology, PubMed, Web (Google))
 
Reference :  P. Mukherjee, H. Li, I. Sevrioukova, G. Chreifi, P. Martasek, L. J. Roman, T. L. Poulos, R. B. Silverman
Novel 2, 4-Disubstituted Pyrimidines As Potent, Selective, And Cell-Permeable Inhibitors Of Neuronal Nitric Oxide Synthase.
J. Med. Chem. V. 58 1067 2015
PubMed-ID: 25489882  |  Reference-DOI: 10.1021/JM501719E

(-) Compounds

Molecule 1 - NITRIC OXIDE SYNTHASE, ENDOTHELIAL
    ChainsA, B
    EC Number1.14.13.39
    EngineeredYES
    Expression SystemESCHERICHIA COLI
    Expression System StrainBL21(DE3)
    Expression System Taxid469008
    Expression System VectorPCWORI
    Expression System Vector TypePLASMID
    FragmentHEME DOMAIN, UNP RESIDUES 40-482
    Organism CommonCATTLE
    Organism ScientificBOS TAURUS
    Organism Taxid9913
    SynonymCONSTITUTIVE NOS, CNOS, EC-NOS, ENDOTHELIAL NOS, ENOS, NOS TYPE III, NOSIII, ENDOTHELIAL NITRIC OXIDE SYNTHASE

 Structural Features

(-) Chains, Units

  12
Asymmetric/Biological Unit AB

Summary Information (see also Sequences/Alignments below)

(-) Ligands, Modified Residues, Ions  (8, 15)

Asymmetric/Biological Unit (8, 15)
No.NameCountTypeFull Name
1ACT2Ligand/IonACETATE ION
2CAS2Mod. Amino AcidS-(DIMETHYLARSENIC)CYSTEINE
3GOL2Ligand/IonGLYCEROL
4H4B2Ligand/Ion5,6,7,8-TETRAHYDROBIOPTERIN
5HEM2Ligand/IonPROTOPORPHYRIN IX CONTAINING FE
6MTL2Ligand/IonD-MANNITOL
7OLW2Ligand/Ion3-[({2-[2-(1H-IMIDAZOL-1-YL)PYRIMIDIN-4-YL]ETHYL}AMINO)METHYL]BENZONITRILE
8ZN1Ligand/IonZINC ION

(-) Sites  (13, 13)

Asymmetric Unit (13, 13)
No.NameEvidenceResiduesDescription
01AC1SOFTWARETRP A:180 , CYS A:186 , VAL A:187 , GLY A:188 , SER A:228 , PHE A:355 , SER A:356 , TRP A:358 , GLU A:363 , TRP A:449 , PHE A:475 , TYR A:477 , H4B A:600 , OLW A:800 , HOH A:2286BINDING SITE FOR RESIDUE HEM A 500
02AC2SOFTWARESER A:104 , ARG A:367 , ALA A:448 , TRP A:449 , HEM A:500 , GOL A:880 , HOH A:2038 , HOH A:2223 , HOH A:2268 , TRP B:447 , PHE B:462 , HIS B:463BINDING SITE FOR RESIDUE H4B A 600
03AC3SOFTWAREVAL A:106 , LEU A:107 , GLN A:249 , PRO A:336 , VAL A:338 , TYR A:477 , HEM A:500 , GOL A:880BINDING SITE FOR RESIDUE OLW A 800
04AC4SOFTWARETRP A:358 , VAL A:420 , SER A:428 , HOH A:2104 , HOH A:2287BINDING SITE FOR RESIDUE ACT A 860
05AC5SOFTWARESER A:248 , ALA A:268 , ASN A:269 , GLU A:271 , ILE A:272 , ASN A:340 , ASP A:480 , HOH A:2153 , HOH A:2156 , HOH A:2174BINDING SITE FOR RESIDUE MTL A 870
06AC6SOFTWAREVAL A:106 , ARG A:367 , HIS A:373 , H4B A:600 , OLW A:800 , TRP B:76BINDING SITE FOR RESIDUE GOL A 880
07AC7SOFTWARETRP B:180 , ARG B:185 , CYS B:186 , SER B:228 , PHE B:355 , SER B:356 , GLY B:357 , TRP B:358 , GLU B:363 , TRP B:449 , PHE B:475 , TYR B:477 , H4B B:600 , OLW B:800 , HOH B:2161 , HOH B:2210 , HOH B:2211BINDING SITE FOR RESIDUE HEM B 500
08AC8SOFTWARETRP A:447 , PHE A:462 , HOH A:2276 , SER B:104 , ARG B:367 , ALA B:448 , TRP B:449 , HEM B:500 , GOL B:880 , HOH B:2026 , HOH B:2168 , HOH B:2200BINDING SITE FOR RESIDUE H4B B 600
09AC9SOFTWAREVAL B:106 , LEU B:107 , GLN B:249 , PRO B:336 , VAL B:338 , TYR B:477 , HEM B:500 , MTL B:870 , GOL B:880BINDING SITE FOR RESIDUE OLW B 800
10BC1SOFTWARETRP B:358 , VAL B:420 , SER B:428 , HOH B:2076 , HOH B:2212BINDING SITE FOR RESIDUE ACT B 860
11BC2SOFTWARESER B:248 , ARG B:252 , ALA B:268 , ASN B:269 , GLU B:271 , ILE B:272 , ASN B:340 , ASP B:480 , OLW B:800 , HOH B:2134 , HOH B:2135BINDING SITE FOR RESIDUE MTL B 870
12BC3SOFTWAREHOH A:2276 , VAL B:106 , ARG B:367 , HIS B:373 , H4B B:600 , OLW B:800BINDING SITE FOR RESIDUE GOL B 880
13BC4SOFTWARECYS A:96 , CYS A:101 , CYS B:96 , CYS B:101BINDING SITE FOR RESIDUE ZN A1483

(-) SS Bonds  (0, 0)

(no "SS Bond" information available for 4D39)

(-) Cis Peptide Bonds  (2, 2)

Asymmetric/Biological Unit
No.Residues
1Ser A:472 -Pro A:473
2Ser B:472 -Pro B:473

 Sequence-Structure Mapping

(-) SAPs(SNPs)/Variants  (0, 0)

(no "SAP(SNP)/Variant" information available for 4D39)

(-) PROSITE Motifs  (0, 0)

(no "PROSITE Motif" information available for 4D39)

(-) Exons   (0, 0)

(no "Exon" information available for 4D39)

(-) Sequences/Alignments

Asymmetric/Biological Unit
   Reformat: Number of residues per line =  ('0' or empty: single-line sequence representation)
  Number of residues per labelling interval =   
  UniProt sequence: complete  aligned part    
   Show mapping: SCOP domains CATH domains Pfam domains Secondary structure (by author)
SAPs(SNPs) PROSITE motifs Exons
(details for a mapped element are shown in a popup box when the mouse pointer rests over it)
Chain A from PDB  Type:PROTEIN  Length:405
                                                                                                                                                                                                                                                                                                                                                                                                                                                     
               SCOP domains --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SCOP domains
               CATH domains --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- CATH domains
               Pfam domains --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Pfam domains
         Sec.struct. author .....eee......eee.hhhhhh...................hhhhhhhhhhhhhhhhhhhh....hhhhhhhhhhhhhhhhhhh....hhhhhhhhhhhhhhh.....hhhhh...eeee.....hhhhhhhhhhhhhhhhhhhhh...eeee...........ee.........eee.....eee...hhhhhhhhhhh.............eeee......eee..hhhhh.eee.......hhhhhh.eee...ee...eeee..eee....ee...hhhhhhhhhhhh.....hhhhhhhhh.....hhhhhhhhhhhhhhhhhhhhhhhhh.....hhhhhhhhhhhhhhhhhhhhh....hhhhhh...hhhhhhhhh..........eee...... Sec.struct. author
                 SAPs(SNPs) --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SAPs(SNPs)
                    PROSITE --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- PROSITE
                 Transcript --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Transcript
                 4d39 A  67 GPKFPRVKNWELGSITYDTLCAQSQQDGPCTPRRCLGSLVLPRPAEQLLSQARDFINQYYSSIKRSGSQAHEERLQEVEAEVASTGTYHLRESELVFGAKQAWRNAPRCVGRIQWGKLQVFDARDCSSAQEMFTYICNHIKYATNRGNLRSAITVFPQRAPGRGDFRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDEAPELFVLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFSAAPFSGWYMSTEIGTRNLCDPHRYNILEDVAVcMDLDTRTTSSLWKDKAAVEINLAVLHSFQLAKVTIVDHHAATVSFMKHLDNEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYILSPAFRYQPDPW 482
                                    76        86        96       106  ||   127       137       147       157       167       177       187       197       207       217       227       237       247       257       267       277       287       297       307       317       327       337       347       357       367       377      |387       397       407       417       427       437       447       457       467       477     
                                                                    109|                                                                                                                                                                                                                                                                    384-CAS                                                                                              
                                                                     121                                                                                                                                                                                                                                                                                                                                                                         

Chain B from PDB  Type:PROTEIN  Length:404
                                                                                                                                                                                                                                                                                                                                                                                                                                                    
               SCOP domains -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SCOP domains
               CATH domains -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- CATH domains
               Pfam domains -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Pfam domains
         Sec.struct. author ...eee......eee.hhhhhh....................hhhhhhhhhhhhhhhhhhhh....hhhhhhhhhhhhhhhhhhh....hhhhhhhhhhhhhhh.....hhhhh...eeee.....hhhhhhhhhhhhhhhhhhhhh...eeee...........ee.........eee.....eee...hhhhhhhhhhh.............eeee......eee..hhhhh.eee.....hhhhhhhh.eee...ee...eeee..eee....ee...hhhhhhhhhhhh.....hhhhhhhhh.....hhhhhhhhhhhhhhhhhhhhhhhhhh....hhhhhhhhhhhhhhhhhhhhh....hhhhhh...hhhhhhhhh..........eee...... Sec.struct. author
                 SAPs(SNPs) -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- SAPs(SNPs)
                    PROSITE -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- PROSITE
                 Transcript -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Transcript
                 4d39 B  69 KFPRVKNWELGSITYDTLCAQSQQDGPCTPRRCLGSLVLPRKPAEQLLSQARDFINQYYSSIKRSGSQAHEERLQEVEAEVASTGTYHLRESELVFGAKQAWRNAPRCVGRIQWGKLQVFDARDCSSAQEMFTYICNHIKYATNRGNLRSAITVFPQRAPGRGDFRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDEAPELFVLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFSAAPFSGWYMSTEIGTRNLCDPHRYNILEDVAVcMDLDTRTTSSLWKDKAAVEINLAVLHSFQLAKVTIVDHHAATVSFMKHLDNEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYILSPAFRYQPDPW 482
                                    78        88        98       108 ||    128       138       148       158       168       178       188       198       208       218       228       238       248       258       268       278       288       298       308       318       328       338       348       358       368       378     | 388       398       408       418       428       438       448       458       468       478    
                                                                   110|                                                                                                                                                                                                                                                                    384-CAS                                                                                              
                                                                    121                                                                                                                                                                                                                                                                                                                                                                         

   Legend:   → Mismatch (orange background)
  - → Gap (green background, '-', border residues have a numbering label)
    → Modified Residue (blue background, lower-case, 'x' indicates undefined single-letter code, labelled with number + name)
  x → Chemical Group (purple background, 'x', labelled with number + name, e.g. ACE or NH2)
  extra numbering lines below/above indicate numbering irregularities and modified residue names etc., number ends below/above '|'

 Classification and Annotation

(-) SCOP Domains  (0, 0)

(no "SCOP Domain" information available for 4D39)

(-) CATH Domains  (0, 0)

(no "CATH Domain" information available for 4D39)

(-) Pfam Domains  (0, 0)

(no "Pfam Domain" information available for 4D39)

(-) Gene Ontology  (27, 27)

Asymmetric/Biological Unit(hide GO term definitions)

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  Cis Peptide Bonds
    Ser A:472 - Pro A:473   [ RasMol ]  
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 Related Entries

(-) Entries Sharing at Least One Protein Chain (UniProt ID)

UniProtKB/Swiss-Prot
        NOS3_BOVIN | P294731d0c 1d0o 1d1v 1d1w 1d1x 1d1y 1dm6 1dm7 1dm8 1dmi 1dmj 1dmk 1ed4 1ed5 1ed6 1foi 1foj 1fol 1foo 1fop 1i83 1nse 1p6l 1p6m 1p6n 1q2o 1rs8 1rs9 1zzs 1zzt 2g6o 2hx2 2nse 3dqs 3dqt 3e7s 3jww 3jwx 3jwy 3jwz 3n5p 3n5q 3n5r 3n5s 3n5t 3nld 3nle 3nlf 3nlg 3nlh 3nli 3nlt 3nlu 3nse 3pnh 3rqo 3rqp 4c3a 4car 4cft 4cty 4ctz 4cu0 4cu1 4cul 4cum 4cun 4cvg 4cwv 4cww 4cwx 4cwy 4cwz 4cx0 4cx1 4cx2 4d33 4d34 4d35 4d36 4d37 4d38 4d3a 4imx 4jsk 4jsl 4jsm 4k5h 4k5i 4k5j 4k5k 4kcp 4kcq 4kcr 4kcs 4luw 4nse 4uh7 4uh8 4uh9 4uha 4upq 4upr 4ups 4upt 5adj 5adk 5adl 5adm 5adn 5fj2 5fj3 5fvy 5fvz 5nse 5uod 6nse 7nse 8nse 9nse

(-) Related Entries Specified in the PDB File

4d2y STRUCTURE OF RAT NEURONAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH N-2-(2-(1H-IMIDAZOL-1-YL) PYRIMIDIN-4-YL)ETHYL-(S,R)-2-(3-FLUOROBENZYL) CYCLOPROPAN-1-AMINE
4d2z STRUCTURE OF RAT NEURONAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH N-2-(2-(1H-IMIDAZOL-1-YL) PYRIMIDIN-4-YL)ETHYL-(R,S)-2-(3-FLUOROBENZYL) CYCLOPROPAN-1-AMINE
4d30 STRUCTURE OF RAT NEURONAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH N-2-(2-(1H-IMIDAZOL-1-YL) PYRIMIDIN-4-YL)ETHYL-3-(PYRIDIN-3-YL)PROPAN-1- AMINE
4d31 STRUCTURE OF RAT NEURONAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH 2-(2-(1H-IMIDAZOL-1-YL) PYRIMIDIN-4-YL)-N-(3-CYANOBENZYL)ETHAN-1-AMINE
4d32 STRUCTURE OF RAT NEURONAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH 3-(3-FLUOROPHENYL)-N-2-(2-( 5-METHYL-1H-IMIDAZOL-1-YL)PYRIMIDIN-4-YL)ETHYLPROPAN -1-AMINE
4d33 STRUCTURE OF BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH (N1-(2-(1H-IMIDAZOL-1- YL)PYRIMIDIN-4-YL)-N2-(3-FLUOROPHENETHYL)ETHANE-1,2 -DIAMINE
4d34 STRUCTURE OF BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH 2-(2-(1H-IMIDAZOL-1-YL )PYRIMIDIN-4-YL)-N-(3-FLUOROPHENETHYL)ETHAN-1-AMINE
4d35 STRUCTURE OF BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH N-2-(2-(1H-IMIDAZOL-1 -YL)PYRIMIDIN-4-YL)ETHYL-3-(3-FLUOROPHENYL)PROPAN-1 -AMINE
4d36 STRUCTURE OF BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH N-2-(2-(1H-IMIDAZOL-1 -YL)PYRIMIDIN-4-YL)ETHYL-3-(3-CHLOROPHENYL)PROPAN-1 -AMINE
4d37 STRUCTURE OF BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITHN-{[(1R,2R)-2-(3- FLUOROPHENYL)CYCLOPROPYL]METHYL}-2-[2-(1H-IMIDAZOL-1- YL)PYRIMIDIN-4-YL]ETHANAMINE
4d38 STRUCTURE OF BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH N-2-(2-(1H-IMIDAZOL-1 -YL)PYRIMIDIN-4-YL)ETHYL-(S,R)-2-(3-FLUOROBENZYL) CYCLOPROPAN-1-AMINE
4d3a STRUCTURE OF BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH 3-(3-FLUOROPHENYL)-N-2 -(2-(5-METHYL-1H-IMIDAZOL-1-YL)PYRIMIDIN-4-YL) ETHYLPROPAN-1-AMINE
4d3b STRUCTURE OF RAT NEURONAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH N1-(2-(1H-IMIDAZOL-1-YL) PYRIMIDIN-4-YL)-N2-(3-FLUOROPHENETHYL)ETHANE-1,2- DIAMINE
4v3u STRUCTURE OF HUMAN NNOS R354A G357D MUTANT HEME DOMAIN IN COMPLEX WITH N-2-(2-(1H-IMIDAZOL-1-YL) PYRIMIDIN-4-YL)ETHYL-3-(PYRIDIN-3-YL)PROPAN-1- AMINE
4v3v STRUCTURE OF RAT NEURONAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH N-(2-(1H-IMIDAZOL-1-YL)-4- PYRIMIDYLMETHYL)-3-(3-FLUOROPHENYL)PROPAN-1-AMINE
4v3w STRUCTURE OF RAT NEURONAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH 2-(2-(1H-IMIDAZOL-1-YL) PYRIMIDIN-4-YL)-N-(3-FLUOROPHENETHYL)ETHAN-1-AMINE
4v3x STRUCTURE OF RAT NEURONAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH N-2-(2-(1H-IMIDAZOL-1-YL) PYRIMIDIN-4-YL)ETHYL-3-(3-FLUOROPHENYL)PROPAN-1- AMINE
4v3y STRUCTURE OF RAT NEURONAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH N-2-(2-(1H-IMIDAZOL-1-YL) PYRIMIDIN-4-YL)ETHYL-3-(3-CHLOROPHENYL)PROPAN-1- AMINE
4v3z STRUCTURE OF RAT NEURONAL NITRIC OXIDE SYNTHASE HEME DOMAIN IN COMPLEX WITH 2-(2-(1H-IMIDAZOL-1-YL) PYRIMIDIN-4-YL)-N-(2-(3-FLUOROPHENYL)CYCLOPROPYLMETHYL) ETHAN-1-AMINE