Structure of PDB 5veu Chain K Binding Site BS01

Receptor Information

>5veu Chain K (length=458) Species: 9606 (Homo sapiens)

TRTHGLFKRLGIPGPTPLPLLGNVLSYRQGLWKFDTECYKKYGKMWGTYE
GQLPVLAITDPDVIRTVLVKECYSVFTNRRSLGPVGFMKSAISLAEDEEW
KRIRSLLSPTFTSGKLKEMFPIIAQYGDVLVRNLRREAEKGKPVTLKDIF
GAYSMDVITGTSFGVNIDSLNNPQDPFVESTKKFLKFGFLDPLFLSIILF
PFLTPVFEALNVSLFPKDTINFLSKSVNRMKKSRLNDKQKHRLDFLQLMI
DSQNALSDLELAAQSIIFIFAGYETTSSVLSFTLYELATHPDVQQKLQKE
IDAVLPNKAPPTYDAVVQMEYLDMVVNETLRLFPVAIRLERTCKKDVEIN
GVFIPKGSMVVIPTYALHHDPKYWTEPEEFRPERFSDSIDPYIYTPFGTG
PRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLDTQGLLQPEKP
IVLKVDSR

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: 5veu Chain K Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5veu The X-Ray Crystal Structure of the Human Mono-Oxygenase Cytochrome P450 3A5-Ritonavir Complex Reveals Active Site Differences between P450s 3A4 and 3A5.
• Resolution: 2.91 Å
• Binding residue (original residue number in PDB): R105 I118 W126 R130 F302 A305 T309 L373 R375 P433 F434 G435 R439 C441 A447
• Binding residue (residue number reindexed from 1): R79 I92 W100 R104 F268 A271 T275 L339 R341 P396 F397 G398 R402 C404 A410
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): T309 F434 C441
• Catalytic site (residue number reindexed from 1): T275 F397 C404
• Enzyme Commision number: 1.14.14.1: unspecific monooxygenase.

Gene Ontology

Molecular Function

• GO:0004497 monooxygenase activity
• GO:0005506 iron ion binding
• GO:0005515 protein binding
• GO:0008401 retinoic acid 4-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:0019825 oxygen binding
• GO:0020037 heme binding
• GO:0046872 metal ion binding
• GO:0050649 testosterone 6-beta-hydroxylase activity
• GO:0070330 aromatase activity
• GO:0101020 estrogen 16-alpha-hydroxylase activity

Biological Process

• GO:0002933 lipid hydroxylation
• GO:0006805 xenobiotic metabolic process
• GO:0008202 steroid metabolic process
• GO:0008210 estrogen metabolic process
• GO:0009822 alkaloid catabolic process
• GO:0042178 xenobiotic catabolic process
• GO:0042572 retinol metabolic process
• GO:0042573 retinoic acid metabolic process
• GO:0046222 aflatoxin metabolic process
• GO:0070989 oxidative demethylation

Cellular Component

• GO:0005783 endoplasmic reticulum
• GO:0005789 endoplasmic reticulum membrane
• GO:0016020 membrane
• GO:0043231 intracellular membrane-bounded organelle

External links

• PDB: RCSB:5veu, PDBe:5veu, PDBj:5veu
• PDBsum: 5veu
• PubMed: 29093019
• UniProt: P20815|CP3A5_HUMAN Cytochrome P450 3A5 (Gene Name=CYP3A5)