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PDBsum entry 1jo9
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Oxidoreductase
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PDB id
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1jo9
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References listed in PDB file
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Key reference
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Title
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Comparison of the hamster and human adrenal p450c17 (17 alpha-Hydroxylase/17,20-Lyase) using site-Directed mutagenesis and molecular modeling.
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Authors
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A.P.Mathieu,
R.J.Auchus,
J.G.Lehoux.
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Ref.
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J Steroid Biochem Mol Biol, 2002,
80,
99.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Secondary reference #1
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Title
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Molecular modeling of human p450c17 (17alpha-Hydroxylase/17,20-Lyase): insights into reaction mechanisms and effects of mutations.
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Authors
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R.J.Auchus,
W.L.Miller.
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Ref.
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Mol Endocrinol, 1999,
13,
1169-1182.
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PubMed id
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