PDBsum entry 2geg

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protein ligands links
Oxidoreductase PDB id
Protein chain
468 a.a.
Theoretical model
PDB id:
Name: Oxidoreductase
Title: Theoretical model of human cyp21 (cytochrome p450, 21- hydroxylase) based on rabbit cyp2c5.
Structure: Cytochrome p450 xxi. Chain: c. Synonym: steroid 21-hydroxylase. 21- ohase. P450-c21. P- 450c21. P450-c21b. Ec:
Source: Homo sapiens. Human
Authors: T.Robins,J.Carlsson,M.Sunnerhagen,A.Wedell,B.Persson
Key ref: T.Robins et al. (2006). Molecular model of human CYP21 based on mammalian CYP2C5: structural features correlate with clinical severity of mutations causing congenital adrenal hyperplasia. Mol Endocrinol, 20, 2946-2964. PubMed id: 16788163
20-Mar-06     Release date:   19-Sep-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08686  (CP21A_HUMAN) -  Steroid 21-hydroxylase
494 a.a.
468 a.a.
Key:    PfamA domain  Secondary structure

 Enzyme reactions 
   Enzyme class: E.C.  - Steroid 21-monooxygenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A C21 steroid + (reduced NADPH--hemoprotein reductase) + O(2) = a 21-hydroxy-C21-steroid + (oxidized NADPH--hemoprotein reductase) + H(2)O
C(21) steroid
Bound ligand (Het Group name = HEM)
matches with 46.00% similarity
+ (reduced NADPH--hemoprotein reductase)
+ O(2)
= 21-hydroxy-C(21)-steroid
+ (oxidized NADPH--hemoprotein reductase)
+ H(2)O
      Cofactor: Heme-thiolate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site


    Key reference    
Mol Endocrinol 20:2946-2964 (2006)
PubMed id: 16788163  
Molecular model of human CYP21 based on mammalian CYP2C5: structural features correlate with clinical severity of mutations causing congenital adrenal hyperplasia.
T.Robins, J.Carlsson, M.Sunnerhagen, A.Wedell, B.Persson.
Enhanced understanding of structure-function relationships of human 21-hydroxylase, CYP21, is required to better understand the molecular causes of congenital adrenal hyperplasia. To this end, a structural model of human CYP21 was calculated based on the crystal structure of rabbit CYP2C5. All but two known allelic variants of missense type, a total of 60 disease-causing mutations and six normal variants, were analyzed using this model. A structural explanation for the corresponding phenotype was found for all but two mutants for which available clinical data are also discrepant with in vitro enzyme activity. Calculations of protein stability of modeled mutants were found to correlate inversely with the corresponding clinical severity. Putative structurally important residues were identified to be involved in heme and substrate binding, redox partner interaction, and enzyme catalysis using docking calculations and analysis of structurally determined homologous cytochrome P450s (CYPs). Functional and structural consequences of seven novel mutations, V139E, C147R, R233G, T295N, L308F, R366C, and M473I, detected in Scandinavian patients with suspected congenital adrenal hyperplasia of different severity, were predicted using molecular modeling. Structural features deduced from the models are in good correlation with clinical severity of CYP21 mutants, which shows the applicability of a modeling approach in assessment of new CYP21 mutations.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21264314 C.Minutolo, A.D.Nadra, C.Fernández, M.Taboas, N.Buzzalino, B.Casali, S.Belli, E.H.Charreau, L.Alba, and L.Dain (2011).
Structure-based analysis of five novel disease-causing mutations in 21-hydroxylase-deficient patients.
  PLoS One, 6, e15899.  
21198393 Y.Yu, J.Wang, X.Huang, Y.Wang, P.Yang, J.Li, S.H.Tsuei, Y.Shen, and Q.Fu (2011).
Molecular characterization of 25 chinese pedigrees with 21-hydroxylase deficiency.
  Genet Test Mol Biomarkers, 15, 137-142.  
20482300 P.Concolino, E.Mello, C.Zuppi, and E.Capoluongo (2010).
Molecular diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency: an update of new CYP21A2 mutations.
  Clin Chem Lab Med, 48, 1057-1062.  
19558493 J.Carlsson, T.Soussi, and B.Persson (2009).
Investigation and prediction of the severity of p53 mutants using parameters from structural calculations.
  FEBS J, 276, 4142-4155.  
19170707 P.Concolino, F.Vendittelli, E.Mello, A.Minucci, C.Carrozza, A.Rossodivita, B.Giardina, C.Zuppi, and E.Capoluongo (2009).
Functional analysis of two rare CYP21A2 mutations detected in Italian patients with a mildest form of congenital adrenal hyperplasia.
  Clin Endocrinol (Oxf), 71, 470-476.  
19152428 P.Concolino, F.Vendittelli, E.Mello, C.Carelli Alinovi, A.Minucci, C.Carrozza, S.A.Santini, C.Zuppi, and E.Capoluongo (2009).
Two novel CYP21A2 missense mutations in Italian patients with 21-hydroxylase deficiency: Identification and functional characterisation.
  IUBMB Life, 61, 229-235.  
19272182 S.Dubey, S.Idicula-Thomas, M.Anwaruddin, C.Saravanan, R.R.Varma, and A.Maitra (2009).
A novel 9-bp insertion detected in steroid 21-hydroxylase gene (CYP21A2): prediction of its structural and functional implications by computational methods.
  J Biomed Sci, 16, 3.  
  19449670 Y.W.Jeske, I.N.McGown, M.Harris, F.G.Bowling, C.S.Choong, D.M.Cowley, and A.M.Cotterill (2009).
21-hydroxylase genotyping in Australasian patients with congenital adrenal hyperplasia.
  J Pediatr Endocrinol Metab, 22, 127-141.  
17573904 A.Baradaran-Heravi, R.Vakili, T.Robins, J.Carlsson, N.Ghaemi, A.A'rabi, and M.R.Abbaszadegan (2007).
Three novel CYP21A2 mutations and their protein modelling in patients with classical 21-hydroxylase deficiency from northeastern Iran.
  Clin Endocrinol (Oxf), 67, 335-341.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.