Structure of PDB 4zgx Chain I Binding Site BS01

Receptor Information

>4zgx Chain I (length=458) Species: 9606 (Homo sapiens)

TVLPFEAMPQHPGNRWLRLLQIWREQGYEHLHLEMHQTFQELGPIFRYPR
MVCVMLPEDVEKLQQVDSLHPCRMILEPWVAYRQHRGHKCGVFLLNGPEW
RFNRLRLNPDVLSPKAVQRFLPMVDAVARDFSQALKKKVLQNARGSLTLD
VQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKSTVQL
MFMPRSLSRWISPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFNRPQHYT
GIVAELLLKAELSLEAIKANSMELTAGSVDTTAFPLLMTLFELARNPDVQ
QILRQESLAAAASISEHPQKATTELPLLRAALKETLRLYPVGLFLERVVS
SDLVLQNYHIPAGTLVQVFLYSLGRNAALFPRPERYNPQRWLDIHVPFGF
GMRQCLGRRLAEAEMLLLLHHVLKHFLVETLTQEDIKMVYSFILRPGTSP
LLTFRAIN

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: 4zgx Chain I Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4zgx Discovery of 4-Aryl-5,6,7,8-tetrahydroisoquinolines as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors: In Vivo Evaluation in Rodents and Cynomolgus Monkeys.
• Resolution: 3.2 Å
• Binding residue (original residue number in PDB): R110 F130 R141 G314 S315 T318 V378 R384 F443 G444 F445 R448 Q449 C450 G452 A456
• Binding residue (residue number reindexed from 1): R73 F93 R104 G277 S278 T281 V341 R347 F398 G399 F400 R403 Q404 C405 G407 A411
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): T318 F443 C450
• Catalytic site (residue number reindexed from 1): T281 F398 C405
• Enzyme Commision number: 1.14.15.4: steroid 11beta-monooxygenase.
  1.14.15.5: corticosterone 18-monooxygenase.

Gene Ontology

Molecular Function

• GO:0004497 monooxygenase activity
• GO:0004507 steroid 11-beta-monooxygenase activity
• GO:0005506 iron ion binding
• GO:0008395 steroid hydroxylase activity
• GO:0016705 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen
• GO:0020037 heme binding
• GO:0046872 metal ion binding
• GO:0047783 corticosterone 18-monooxygenase activity

Biological Process

• GO:0002017 regulation of blood volume by renal aldosterone
• GO:0003091 renal water homeostasis
• GO:0006629 lipid metabolic process
• GO:0006694 steroid biosynthetic process
• GO:0006700 C21-steroid hormone biosynthetic process
• GO:0006704 glucocorticoid biosynthetic process
• GO:0006705 mineralocorticoid biosynthetic process
• GO:0008203 cholesterol metabolic process
• GO:0016125 sterol metabolic process
• GO:0032342 aldosterone biosynthetic process
• GO:0032870 cellular response to hormone stimulus
• GO:0034650 cortisol metabolic process
• GO:0034651 cortisol biosynthetic process
• GO:0035865 cellular response to potassium ion
• GO:0055075 potassium ion homeostasis
• GO:0055078 sodium ion homeostasis
• GO:0071375 cellular response to peptide hormone stimulus
• GO:1901615 organic hydroxy compound metabolic process

Cellular Component

• GO:0005739 mitochondrion
• GO:0005743 mitochondrial inner membrane

External links

• PDB: RCSB:4zgx, PDBe:4zgx, PDBj:4zgx
• PDBsum: 4zgx
• PubMed: 26403853
• UniProt: P19099|C11B2_HUMAN Cytochrome P450 11B2, mitochondrial (Gene Name=CYP11B2)