1kzo
From Proteopedia
(New page: 200px<br /><applet load="1kzo" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kzo, resolution 2.20Å" /> '''PROTEIN FARNESYLTRAN...) |
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| - | [[Image:1kzo.jpg|left|200px]]<br /><applet load="1kzo" size=" | + | [[Image:1kzo.jpg|left|200px]]<br /><applet load="1kzo" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1kzo, resolution 2.20Å" /> | caption="1kzo, resolution 2.20Å" /> | ||
'''PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH FARNESYLATED K-RAS4B PEPTIDE PRODUCT AND FARNESYL DIPHOSPHATE SUBSTRATE BOUND SIMULTANEOUSLY'''<br /> | '''PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH FARNESYLATED K-RAS4B PEPTIDE PRODUCT AND FARNESYL DIPHOSPHATE SUBSTRATE BOUND SIMULTANEOUSLY'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Protein farnesyltransferase (FTase) catalyses the attachment of a farnesyl | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1KZO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with ZN, FAR, FPP and ACY as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Squalene_synthase Squalene synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.21 2.5.1.21] Full crystallographic information is available from [http:// | + | 1KZO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=FAR:'>FAR</scene>, <scene name='pdbligand=FPP:'>FPP</scene> and <scene name='pdbligand=ACY:'>ACY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Squalene_synthase Squalene synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.21 2.5.1.21] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KZO OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Squalene synthase]] | [[Category: Squalene synthase]] | ||
| - | [[Category: Beese, L | + | [[Category: Beese, L S.]] |
| - | [[Category: Casey, P | + | [[Category: Casey, P J.]] |
| - | [[Category: Long, S | + | [[Category: Long, S B.]] |
[[Category: ACY]] | [[Category: ACY]] | ||
[[Category: FAR]] | [[Category: FAR]] | ||
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[[Category: substrate]] | [[Category: substrate]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:39:40 2008'' |
Revision as of 11:39, 21 February 2008
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PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH FARNESYLATED K-RAS4B PEPTIDE PRODUCT AND FARNESYL DIPHOSPHATE SUBSTRATE BOUND SIMULTANEOUSLY
Overview
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.
About this Structure
1KZO is a Protein complex structure of sequences from Rattus norvegicus with , , and as ligands. Active as Squalene synthase, with EC number 2.5.1.21 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 Thu Feb 21 13:39:40 2008
Categories: Protein complex | Rattus norvegicus | Squalene synthase | Beese, L S. | Casey, P J. | Long, S B. | ACY | FAR | FPP | ZN | Caax | Cancer | Farnesyl protein transferase | Farnesyl transferase | Farnesyltransferase | Fpt | Ft | Ftase | Pft | Pftase | Product | Ras | Substrate
