1kzo

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{{STRUCTURE_1kzo| PDB=1kzo | SCENE= }}
{{STRUCTURE_1kzo| PDB=1kzo | SCENE= }}
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'''PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH FARNESYLATED K-RAS4B PEPTIDE PRODUCT AND FARNESYL DIPHOSPHATE SUBSTRATE BOUND SIMULTANEOUSLY'''
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===PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH FARNESYLATED K-RAS4B PEPTIDE PRODUCT AND FARNESYL DIPHOSPHATE SUBSTRATE BOUND SIMULTANEOUSLY===
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==Overview==
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Protein farnesyltransferase (FTase) catalyses the attachment of a farnesyl lipid group to numerous essential signal transduction proteins, including members of the Ras superfamily. The farnesylation of Ras oncoproteins, which are associated with 30% of human cancers, is essential for their transforming activity. FTase inhibitors are currently in clinical trials for the treatment of cancer. Here we present a complete series of structures representing the major steps along the reaction coordinate of this enzyme. From these observations can be deduced the determinants of substrate specificity and an unusual mechanism in which product release requires binding of substrate, analogous to classically processive enzymes. A structural model for the transition state consistent with previous mechanistic studies was also constructed. The processive nature of the reaction suggests the structural basis for the successive addition of two prenyl groups to Rab proteins by the homologous enzyme geranylgeranyltransferase type-II. Finally, known FTase inhibitors seem to differ in their mechanism of inhibiting the enzyme.
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(as it appears on PubMed at http://www.pubmed.gov), where 12374986 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12374986}}
==About this Structure==
==About this Structure==
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[[Category: Ra]]
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[[Category: Substrate]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:22:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 11:22:39 2008''

Revision as of 08:22, 2 July 2008

Image:1kzo.png

Template:STRUCTURE 1kzo

PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH FARNESYLATED K-RAS4B PEPTIDE PRODUCT AND FARNESYL DIPHOSPHATE SUBSTRATE BOUND SIMULTANEOUSLY

Template:ABSTRACT PUBMED 12374986

About this Structure

1KZO is a Protein complex structure of sequences from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Reaction path of protein farnesyltransferase at atomic resolution., Long SB, Casey PJ, Beese LS, Nature. 2002 Oct 10;419(6907):645-50. PMID:12374986

Page seeded by OCA on Wed Jul 2 11:22:39 2008

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