PDBsum entry 4dvq

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chain
(+ 6 more) 463 a.a.
HEM ×12
1CA ×12
SO4 ×9
Waters ×260
PDB id:
Name: Oxidoreductase
Title: Structure of human aldosterone synthase, cyp11b2, in complex deoxycorticosterone
Structure: Cytochrome p450 11b2, mitochondrial. Chain: a, b, c, d, e, f, g, h, i, j, k, l. Synonym: aldosterone synthase, aldos, aldosterone-synthesiz enzyme, cypxib2, cytochrome p-450aldo, cytochrome p-450c18, 18-hydroxylase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: aldosterone synthase, cyp11b2. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.49Å     R-factor:   0.207     R-free:   0.263
Authors: N.Strushkevich,L.Shen,W.Tempel,C.Arrowsmith,A.Edwards,S.A.Us W.Park
Key ref: N.Strushkevich et al. (2013). Structural insights into aldosterone synthase substrate specificity and targeted inhibition. Mol Endocrinol, 27, 315-324. PubMed id: 23322723
23-Feb-12     Release date:   30-Jan-13    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P19099  (C11B2_HUMAN) -  Cytochrome P450 11B2, mitochondrial
503 a.a.
463 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.  - Steroid 11-beta-monooxygenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A steroid + 2 reduced adrenodoxin + O2 + 2 H+ = an 11-beta- hydroxysteroid + 2 oxidized adrenodoxin + H2O
+ 2 × reduced adrenodoxin
+ O(2)
+ 2 × H(+)
= 11-beta- hydroxysteroid
+ 2 × oxidized adrenodoxin
+ H(2)O
      Cofactor: Heme-thiolate
   Enzyme class 2: E.C.  - Corticosterone 18-monooxygenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Corticosterone + 2 reduced adrenodoxin + O2 + 2 H+ = 18-hydroxycorticosterone + 2 oxidized adrenodoxin + H2O
+ 2 × reduced adrenodoxin
+ O(2)
+ 2 × H(+)
Bound ligand (Het Group name = 1CA)
matches with 92.31% similarity
= 18-hydroxycorticosterone
+ 2 × oxidized adrenodoxin
+ H(2)O
      Cofactor: Heme-thiolate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   4 terms 
  Biological process     cellular response to potassium ion   17 terms 
  Biochemical function     oxidoreductase activity     8 terms  


Mol Endocrinol 27:315-324 (2013)
PubMed id: 23322723  
Structural insights into aldosterone synthase substrate specificity and targeted inhibition.
N.Strushkevich, A.A.Gilep, L.Shen, C.H.Arrowsmith, A.M.Edwards, S.A.Usanov, H.W.Park.
Aldosterone is a major mineralocorticoid hormone that plays a key role in the regulation of electrolyte balance and blood pressure. Excess aldosterone levels can arise from dysregulation of the renin-angiotensin-aldosterone system and are implicated in the pathogenesis of hypertension and heart failure. Aldosterone synthase (cytochrome P450 11B2, CYP11B2) is the sole enzyme responsible for the production of aldosterone in humans. Blocking of aldosterone synthesis by mediating aldosterone synthase activity is thus a recently emerging pharmacological therapy for hypertension, yet a lack of structural information has limited this approach. Here, we present the crystal structures of human aldosterone synthase in complex with a substrate deoxycorticosterone and an inhibitor fadrozole. The structures reveal a hydrophobic cavity with specific features associated with corticosteroid recognition. The substrate binding mode, along with biochemical data, explains the high 11β-hydroxylase activity of aldosterone synthase toward both gluco- and mineralocorticoid formation. The low processivity of aldosterone synthase with a high extent of intermediates release might be one of the mechanisms of controlled aldosterone production from deoxycorticosterone. Although the active site pocket is lined by identical residues between CYP11B isoforms, most of the divergent residues that confer additional 18-oxidase activity of aldosterone synthase are located in the I-helix (vicinity of the O(2) activation path) and loops around the H-helix (affecting an egress channel closure required for retaining intermediates in the active site). This intrinsic flexibility is also reflected in isoform-selective inhibitor binding. Fadrozole binds to aldosterone synthase in the R-configuration, using part of the active site cavity pointing toward the egress channel. The structural organization of aldosterone synthase provides critical insights into the molecular mechanism of catalysis and enables rational design of more specific antihypertensive agents.