Structure of PDB 5veu Chain A Binding Site BS02

Receptor Information

>5veu Chain A (length=462) Species: 9606 (Homo sapiens)

TRTHGLFKRLGIPGPTPLPLLGNVLSYRQGLWKFDTECYKKYGKMWGTYE
GQLPVLAITDPDVIRTVLVKECYSVFTNRRSLGPVGFMKSAISLAEDEEW
KRIRSLLSPTFTSGKLKEMFPIIAQYGDVLVRNLRREAEKGKPVTLKDIF
GAYSMDVITGTSFGVNIDSLNNPQDPFVESTKKFLKFGFLDPLFLSIILF
PFLTPVFEALNVSLFPKDTINFLSKSVNRMKKSRLNDKQKHRLDFLQLMI
DSQNSALSDLELAAQSIIFIFAGYETTSSVLSFTLYELATHPDVQQKLQK
EIDAVLPNKAPPTYDAVVQMEYLDMVVNETLRLFPVAIRLERTCKKDVEI
NGVFIPKGSMVVIPTYALHHDPKYWTEPEEFRPERFSKKKDSIDPYIYTP
FGTGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLDTQGLLQ
PEKPIVLKVDSR

Ligand information

• Ligand ID: RIT
• InChI: InChI=1S/C37H48N6O5S2/c1-24(2)33(42-36(46)43(5)20-29-22-49-35(40-29)25(3)4)34(45)39-28(16-26-12-8-6-9-13-26)18-32(44)31(17-27-14-10-7-11-15-27)41-37(47)48-21-30-19-38-23-50-30/h6-15,19,22-25,28,31-33,44H,16-18,20-21H2,1-5H3,(H,39,45)(H,41,47)(H,42,46)/t28-,31-,32-,33-/m0/s1
• InChIKey: NCDNCNXCDXHOMX-XGKFQTDJSA-N
• SMILES:
  OpenEye OEToolkits 1.7.0: CC(C)c1nc(cs1)CN(C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](Cc2ccccc2)C[C@@H]([C@H](Cc3ccccc3)NC(=O)OCc4cncs4)O
  OpenEye OEToolkits 1.7.0: CC(C)c1nc(cs1)CN(C)C(=O)NC(C(C)C)C(=O)NC(Cc2ccccc2)CC(C(Cc3ccccc3)NC(=O)OCc4cncs4)O
  CACTVS 3.370: CC(C)[CH](NC(=O)N(C)Cc1csc(n1)C(C)C)C(=O)N[CH](C[CH](O)[CH](Cc2ccccc2)NC(=O)OCc3scnc3)Cc4ccccc4
  CACTVS 3.370: CC(C)[C@H](NC(=O)N(C)Cc1csc(n1)C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](Cc2ccccc2)NC(=O)OCc3scnc3)Cc4ccccc4
  ACDLabs 12.01: O=C(OCc1scnc1)NC(Cc2ccccc2)C(O)CC(NC(=O)C(NC(=O)N(Cc3nc(sc3)C(C)C)C)C(C)C)Cc4ccccc4
• Formula: C37 H48 N6 O5 S2
• Name: RITONAVIR;
  A-84538
• ChEMBL: CHEMBL163
• DrugBank: DB00503
• ZINC: ZINC000003944422
• PDB chain: 5veu Chain A Residue 602

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): F210 F213 F215 F241 I301 F304 T309 A370 G480
• Binding residue (residue number reindexed from 1): F184 F187 F189 F215 I268 F271 T276 A337 G447
• Annotation score: 1
• Binding affinity: BindingDB: Ki=120nM

Enzymatic activity

• Catalytic site (original residue number in PDB): T309 F434 C441
• Catalytic site (residue number reindexed from 1): T276 F401 C408
• 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)