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PDBsum entry 1jo9
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Oxidoreductase PDB id
1jo9

 

 

 

 

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Contents
Protein chain
454 a.a.
Ligands
HEM
Theoretical model
PDB id:
1jo9
Name: Oxidoreductase
Title: Computational model of hamster p450c17
Structure: Cytochrome p450c17. Chain: a. Synonym: 17alpha-hydroxylase/17,20-lyase, cyp17. Ec: 1.14.99.9
Source: Mesocricetus auratus. Hamster
Authors: A.P.Mathieu,R.J.Auchus,J.G.Lehoux
Key ref: A.P.Mathieu et al. (2002). Comparison of the hamster and human adrenal P450c17 (17 alpha-hydroxylase/17,20-lyase) using site-directed mutagenesis and molecular modeling. J Steroid Biochem Mol Biol, 80, 99. PubMed id: 11867269 DOI: 10.1016/S0960-0760(01)00172-8
Date:
27-Jul-01     Release date:   20-Mar-02    
PROCHECK
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 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 454 a.a.
Key:    Secondary structure

 

 
DOI no: 10.1016/S0960-0760(01)00172-8 J Steroid Biochem Mol Biol 80:99 (2002)
PubMed id: 11867269  
 
 
Comparison of the hamster and human adrenal P450c17 (17 alpha-hydroxylase/17,20-lyase) using site-directed mutagenesis and molecular modeling.
A.P.Mathieu, R.J.Auchus, J.G.LeHoux.
 
  ABSTRACT  
 
In order to understand the activity specificity of the hamster cytochrome P450 17 alpha-hydroxylase/17,20-lyase (P450c17), we have studied its structure/activity using three hamster P450c17 recombinant mutants (T202N/D240N/D407H). In transiently transfected COS-1 cells, the mutation T202N reduced 17 alpha-hydroxylation of pregnenolone and progesterone to 24 and 44% of wild type (WT), respectively, followed by reduced 17,20-cleavage to 71 and 67%, respectively. On the other hand, the mutation D240N decreased specifically 17,20-lyase activity to 61% of WT when incubated with pregnenolone while the mutation D407H only decreased 17 alpha-hydroxylation to 46% when incubated with progesterone.To comprehend the altered activity profiles of these hamster P450c17 mutants, we have elaborated a 3D model of the hamster P450c17 and compared it to our preceding model of the human P450c17. Analysis of the mutants with this model showed that, without direct contact to the substrates, these mutations transmit structural changes to the active site. By analogy, these results support the concept that any cellular changes modifying the external structure of P450c17, such as phosphorylation, could have influence on its active site and enzymatic activities.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20178799 J.C.Sivils, I.Gonzalez, and L.J.Bain (2010).
Mice lacking Mrp1 have reduced testicular steroid hormone levels and alterations in steroid biosynthetic enzymes.
  Gen Comp Endocrinol, 167, 51-59.  
19267349 J.A.Locke, L.Fazli, H.Adomat, J.Smyl, K.Weins, A.A.Lubik, D.B.Hales, C.C.Nelson, M.E.Gleave, and E.S.Tomlinson Guns (2009).
A novel communication role for CYP17A1 in the progression of castration-resistant prostate cancer.
  Prostate, 69, 928-937.  
15030474 M.Amichot, S.Tarès, A.Brun-Barale, L.Arthaud, J.M.Bride, and J.B.Bergé (2004).
Point mutations associated with insecticide resistance in the Drosophila cytochrome P450 Cyp6a2 enable DDT metabolism.
  Eur J Biochem, 271, 1250-1257.  
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.

 

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