Structure of PDB 4gqs Chain C Binding Site BS01

Receptor Information

>4gqs Chain C (length=462) Species: 9606 (Homo sapiens)

LPPGPTPLPVIGNILQIDIKDVSKSLTNLSKIYGPVFTLYFGLERMVVLH
GYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRWKEIRRFSL
MTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVI
CSIIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPG
THNKLLKNLAFMESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQ
QSEFTIENLVITAADLLGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIE
RVVGRNRSPCMQDRGHMPYTDAVVHEVQRYIDLIPTSLPHAVTCDVKFRN
YLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFKKSNYFMPF
SAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFAS
VPPFYQLCFIPI

Ligand information

• Ligand ID: HEM
• InChI: InChI=1S/C34H34N4O4.Fe/c1-7-21-17(3)25-13-26-19(5)23(9-11-33(39)40)31(37-26)16-32-24(10-12-34(41)42)20(6)28(38-32)15-30-22(8-2)18(4)27(36-30)14-29(21)35-25;/h7-8,13-16H,1-2,9-12H2,3-6H3,(H4,35,36,37,38,39,40,41,42);/q;+2/p-2/b25-13-,26-13-,27-14-,28-15-,29-14-,30-15-,31-16-,32-16-;
• InChIKey: KABFMIBPWCXCRK-RGGAHWMASA-L
• SMILES:
  OpenEye OEToolkits 1.7.6: Cc1c2n3c(c1CCC(=O)O)C=C4C(=C(C5=[N]4[Fe]36[N]7=C(C=C8N6C(=C5)C(=C8C)C=C)C(=C(C7=C2)C)C=C)C)CCC(=O)O
  CACTVS 3.385: CC1=C(CCC(O)=O)C2=Cc3n4[Fe]5|6|N2=C1C=c7n5c(=CC8=N|6C(=Cc4c(C)c3CCC(O)=O)C(=C8C=C)C)c(C)c7C=C
  ACDLabs 12.01: C=1c3c(c(c4C=C5C(=C(C=6C=C7C(=C(C8=CC=2C(=C(C=1N=2[Fe](n34)(N5=6)N78)CCC(=O)O)C)\C=C)C)\C=C)C)C)CCC(=O)O
• Formula: C34 H32 Fe N4 O4
• Name: PROTOPORPHYRIN IX CONTAINING FE;
  HEME
• DrugBank: DB18267
• PDB chain: 4gqs Chain C Residue 501

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4gqs Structural Characterization of Human Cytochrome P450 2C19: ACTIVE SITE DIFFERENCES BETWEEN P450s 2C8, 2C9, AND 2C19.
• Resolution: 2.87 Å
• Binding residue (original residue number in PDB): R97 I112 W120 R124 I178 A297 G298 T301 T302 T305 S365 H368 P427 F428 S429 R433 C435 G437 A441
• Binding residue (residue number reindexed from 1): R69 I84 W92 R96 I150 A269 G270 T273 T274 T277 S337 H340 P399 F400 S401 R405 C407 G409 A413
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): T301 F428 C435
• Catalytic site (residue number reindexed from 1): T273 F400 C407
• Enzyme Commision number: 1.14.14.1: unspecific monooxygenase.
  1.14.14.51: (S)-limonene 6-monooxygenase.
  1.14.14.52: (S)-limonene 7-monooxygenase.
  1.14.14.53: (R)-limonene 6-monooxygenase.
  1.14.14.75: fenbendazole monooxygenase (4'-hydroxylating).

Gene Ontology

Molecular Function

• GO:0004497 monooxygenase activity
• GO:0005506 iron ion binding
• GO:0008392 arachidonate epoxygenase activity
• GO:0008395 steroid hydroxylase activity
• GO:0016491 oxidoreductase activity
• GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
• GO:0016712 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
• GO:0018675 (S)-limonene 6-monooxygenase activity
• GO:0018676 (S)-limonene 7-monooxygenase activity
• GO:0019825 oxygen binding
• GO:0019899 enzyme binding
• GO:0020037 heme binding
• GO:0046872 metal ion binding
• GO:0052741 (R)-limonene 6-monooxygenase activity
• GO:0070330 aromatase activity
• GO:0120319 long-chain fatty acid omega-1 hydroxylase activity

Biological Process

• GO:0001676 long-chain fatty acid metabolic process
• GO:0006631 fatty acid metabolic process
• GO:0006805 xenobiotic metabolic process
• GO:0008202 steroid metabolic process
• GO:0016098 monoterpenoid metabolic process
• GO:0019373 epoxygenase P450 pathway
• GO:0042178 xenobiotic catabolic process
• GO:0097267 omega-hydroxylase P450 pathway

Cellular Component

• GO:0005737 cytoplasm
• GO:0005783 endoplasmic reticulum
• GO:0005789 endoplasmic reticulum membrane
• GO:0005886 plasma membrane
• GO:0016020 membrane
• GO:0043231 intracellular membrane-bounded organelle

External links

• PDB: RCSB:4gqs, PDBe:4gqs, PDBj:4gqs
• PDBsum: 4gqs
• PubMed: 23118231
• UniProt: P33261|CP2CJ_HUMAN Cytochrome P450 2C19 (Gene Name=CYP2C19)