File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Mutation of proline 409 to arginine in the meander region of cytochrome P450c17 causes severe 17α-hydroxylase deficiency

TitleMutation of proline 409 to arginine in the meander region of cytochrome P450c17 causes severe 17α-hydroxylase deficiency
Authors
Issue Date2001
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ymgme
Citation
Molecular Genetics And Metabolism, 2001, v. 72 n. 3, p. 254-259 How to Cite?
AbstractWe elucidated the molecular basis of 17α-hydroxylase deficiency in a Chinese patient with male pseudohermaphroditism. The patient is a compound heterozygote, carrying two different mutant alleles in the CYP17 gene. The first mutation, g.6333-6341delGACTCTTTCA, located in exon 8, was reported in a Thai patient living in a rural village in Thailand. We suggest that g. 6333-6341del-GACTCTTTCA may be a prevalent mutation causing P450c17 deficiency in Southeast Asia. The second mutation is a mlssense mutation, g. 5582C>G, located in exon 7, changing the codon 409 from CCG to CGG, and changing the coded amino acid from proline to arginine, i.e., P409R. This proline residue is conserved in P450c17 of other species and other human P450 proteins. Site-directed mutagenesis, in vitro expression, and functional analysis of the P409R mutant in COS-1 cells show that it has a complete lack of 17α-hydroxylase activity. The pro. line residue probably causes a turn in the meander region of P450c17, and we hypothesize, by comparison to homologous proteins, that the change in the protein conformation may abolish heine incorporation or may prevent P450c17 from interacting with electron donors. © 2001 Academic Press.
Persistent Identifierhttp://hdl.handle.net/10722/148259
ISSN
2015 Impact Factor: 3.093
2015 SCImago Journal Rankings: 1.520
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLam, CWen_US
dc.contributor.authorArlt, Wen_US
dc.contributor.authorChan, CKen_US
dc.contributor.authorHonour, JWen_US
dc.contributor.authorLin, CJen_US
dc.contributor.authorTong, SFen_US
dc.contributor.authorChoy, KWen_US
dc.contributor.authorMiller, WLen_US
dc.date.accessioned2012-05-29T06:11:50Z-
dc.date.available2012-05-29T06:11:50Z-
dc.date.issued2001en_US
dc.identifier.citationMolecular Genetics And Metabolism, 2001, v. 72 n. 3, p. 254-259en_US
dc.identifier.issn1096-7192en_US
dc.identifier.urihttp://hdl.handle.net/10722/148259-
dc.description.abstractWe elucidated the molecular basis of 17α-hydroxylase deficiency in a Chinese patient with male pseudohermaphroditism. The patient is a compound heterozygote, carrying two different mutant alleles in the CYP17 gene. The first mutation, g.6333-6341delGACTCTTTCA, located in exon 8, was reported in a Thai patient living in a rural village in Thailand. We suggest that g. 6333-6341del-GACTCTTTCA may be a prevalent mutation causing P450c17 deficiency in Southeast Asia. The second mutation is a mlssense mutation, g. 5582C>G, located in exon 7, changing the codon 409 from CCG to CGG, and changing the coded amino acid from proline to arginine, i.e., P409R. This proline residue is conserved in P450c17 of other species and other human P450 proteins. Site-directed mutagenesis, in vitro expression, and functional analysis of the P409R mutant in COS-1 cells show that it has a complete lack of 17α-hydroxylase activity. The pro. line residue probably causes a turn in the meander region of P450c17, and we hypothesize, by comparison to homologous proteins, that the change in the protein conformation may abolish heine incorporation or may prevent P450c17 from interacting with electron donors. © 2001 Academic Press.en_US
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ymgmeen_US
dc.relation.ispartofMolecular Genetics and Metabolismen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAdrenal Hyperplasia, Congenitalen_US
dc.subject.meshDna Mutational Analysisen_US
dc.subject.meshDisorders Of Sex Development - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshMutagenesis, Site-Directeden_US
dc.subject.meshMutation, Missenseen_US
dc.subject.meshSequence Analysis, Dnaen_US
dc.subject.meshSteroid 17-Alpha-Hydroxylase - Geneticsen_US
dc.titleMutation of proline 409 to arginine in the meander region of cytochrome P450c17 causes severe 17α-hydroxylase deficiencyen_US
dc.typeArticleen_US
dc.identifier.emailLam, CW:ching-wanlam@pathology.hku.hken_US
dc.identifier.authorityLam, CW=rp00260en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1006/mgme.2000.3134en_US
dc.identifier.pmid11243732-
dc.identifier.scopuseid_2-s2.0-0035718922en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035718922&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume72en_US
dc.identifier.issue3en_US
dc.identifier.spage254en_US
dc.identifier.epage259en_US
dc.identifier.isiWOS:000167615200009-
dc.publisher.placeUnited Statesen_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats