Structure of PDB 6xz8 Chain A Binding Site BS01

Receptor Information

>6xz8 Chain A (length=465) Species: 9606 (Homo sapiens)

TVLPFEAMPQHPGNRWLRLLQIWREQGYEHLHLEMHQTFQELGPIFRYNL
GGPRMVCVMLPEDVEKLQQVDSLHPCRMILEPWVAYRQHRGHKCGVFLLN
GPEWRFNRLRLNPDVLSPKAVQRFLPMVDAVARDFSQALKKKVLQNARGS
LTLDVQPSIFHYTIEASNLALFGERLGLVGHSPSSASLNFLHALEVMFKS
TVQLMFMPRSLSRWISPKVWKEHFEAWDCIFQYGDNCIQKIYQELAFNRP
QHYTGIVAELLLKAELSLEAIKANSMELTAGSVDTTAFPLLMTLFELARN
PDVQQILRQESLAAAASISEHPQKATTELPLLRAALKETLRLYPVGLFLE
RVVSSDLVLQNYHIPAGTLVQVFLYSLGRNAALFPRPERYNPQRWLDINF
HHVPFGFGMRQCLGRRLAEAEMLLLLHHVLKHFLVETLTQEDIKMVYSFI
LRPGTSPLLTFRAIN

Ligand information

• Ligand ID: HEC
• 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,9-12H2,1-6H3,(H,39,40)(H,41,42);/q-4;+4/b21-7?,22-8?,26-13-,29-14-,30-15-,31-16-;
• InChIKey: HXQIYSLZKNYNMH-LJNAALQVSA-N
• SMILES:
  ACDLabs 10.04: O=C(O)CCC1=C(C2=CC6=C(C(=C/C)\C5=CC4=C(C(\C3=Cc7c(c(c8C=C1N2[Fe](N34)(N56)n78)CCC(=O)O)C)=C/C)C)C)C
  OpenEye OEToolkits 1.5.0: CC=C1C(=C2C=C3C(=CC)C(=C4N3[Fe]56N2C1=Cc7n5c(c(c7C)CCC(=O)O)C=C8N6C(=C4)C(=C8CCC(=O)O)C)C)C
  CACTVS 3.341: C\C=C1/C(=C2C=C3N4C(=Cc5n6c(C=C7N8C(=C(C)\C7=C/C)C=C1N2[Fe@@]468)c(C)c5CCC(O)=O)C(=C3C)CCC(O)=O)C
  CACTVS 3.341: CC=C1C(=C2C=C3N4C(=Cc5n6c(C=C7N8C(=C(C)C7=CC)C=C1N2[Fe]468)c(C)c5CCC(O)=O)C(=C3C)CCC(O)=O)C
• Formula: C34 H34 Fe N4 O4
• Name: HEME C
• PDB chain: 6xz8 Chain A Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6xz8 Discovery of 3-Pyridyl Isoindolin-1-one Derivatives as Potent, Selective, and Orally Active Aldosterone Synthase (CYP11B2) Inhibitors.
• Resolution: 3.0 Å
• Binding residue (original residue number in PDB): R110 V129 F130 R141 G314 S315 T318 R384 P442 F443 G444 F445 R448 C450 G452
• Binding residue (residue number reindexed from 1): R77 V96 F97 R108 G281 S282 T285 R351 P404 F405 G406 F407 R410 C412 G414
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): T318 F443 C450
• Catalytic site (residue number reindexed from 1): T285 F405 C412
• 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:6xz8, PDBe:6xz8, PDBj:6xz8
• PDBsum: 6xz8
• PubMed: 32530624
• UniProt: P19099|C11B2_HUMAN Cytochrome P450 11B2, mitochondrial (Gene Name=CYP11B2)