1n4r: Difference between revisions
New page: left|200px<br /><applet load="1n4r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n4r, resolution 2.80Å" /> '''Protein Geranylgeran... |
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[[Image:1n4r.gif|left|200px]]<br /><applet load="1n4r" size=" | [[Image:1n4r.gif|left|200px]]<br /><applet load="1n4r" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1n4r, resolution 2.80Å" /> | caption="1n4r, resolution 2.80Å" /> | ||
'''Protein Geranylgeranyltransferase type-I Complexed with a Geranylgeranylated KKKSKTKCVIL Peptide Product'''<br /> | '''Protein Geranylgeranyltransferase type-I Complexed with a Geranylgeranylated KKKSKTKCVIL Peptide Product'''<br /> | ||
==Overview== | ==Overview== | ||
Protein geranylgeranyltransferase type-I (GGTase-I), one of two CaaX | Protein geranylgeranyltransferase type-I (GGTase-I), one of two CaaX prenyltransferases, is an essential enzyme in eukaryotes. GGTase-I catalyzes C-terminal lipidation of >100 proteins, including many GTP- binding regulatory proteins. We present the first structural information for mammalian GGTase-I, including a series of substrate and product complexes that delineate the path of the chemical reaction. These structures reveal that all protein prenyltransferases share a common reaction mechanism and identify specific residues that play a dominant role in determining prenyl group specificity. This hypothesis was confirmed by converting farnesyltransferase (15-C prenyl substrate) into GGTase-I (20-C prenyl substrate) with a single point mutation. GGTase-I discriminates against farnesyl diphosphate (FPP) at the product turnover step through the inability of a 15-C FPP to displace the 20-C prenyl-peptide product. Understanding these key features of specificity is expected to contribute to optimization of anti-cancer and anti-parasite drugs. | ||
==About this Structure== | ==About this Structure== | ||
1N4R 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, CL, SO4, MES and TTH as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1N4R 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=CL:'>CL</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=MES:'>MES</scene> and <scene name='pdbligand=TTH:'>TTH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N4R OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Beese, L | [[Category: Beese, L S.]] | ||
[[Category: Casey, P | [[Category: Casey, P J.]] | ||
[[Category: Reid, T | [[Category: Reid, T S.]] | ||
[[Category: Taylor, J | [[Category: Taylor, J S.]] | ||
[[Category: CL]] | [[Category: CL]] | ||
[[Category: MES]] | [[Category: MES]] | ||
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[[Category: rap2b]] | [[Category: rap2b]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:02:17 2008'' | ||
Revision as of 12:02, 21 February 2008
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Protein Geranylgeranyltransferase type-I Complexed with a Geranylgeranylated KKKSKTKCVIL Peptide Product
Overview
Protein geranylgeranyltransferase type-I (GGTase-I), one of two CaaX prenyltransferases, is an essential enzyme in eukaryotes. GGTase-I catalyzes C-terminal lipidation of >100 proteins, including many GTP- binding regulatory proteins. We present the first structural information for mammalian GGTase-I, including a series of substrate and product complexes that delineate the path of the chemical reaction. These structures reveal that all protein prenyltransferases share a common reaction mechanism and identify specific residues that play a dominant role in determining prenyl group specificity. This hypothesis was confirmed by converting farnesyltransferase (15-C prenyl substrate) into GGTase-I (20-C prenyl substrate) with a single point mutation. GGTase-I discriminates against farnesyl diphosphate (FPP) at the product turnover step through the inability of a 15-C FPP to displace the 20-C prenyl-peptide product. Understanding these key features of specificity is expected to contribute to optimization of anti-cancer and anti-parasite drugs.
About this Structure
1N4R is a Protein complex structure of sequences from Rattus norvegicus with ZN, CL, SO4, MES and TTH as ligands. Full crystallographic information is available from OCA.
Reference
Structure of mammalian protein geranylgeranyltransferase type-I., Taylor JS, Reid TS, Terry KL, Casey PJ, Beese LS, EMBO J. 2003 Nov 17;22(22):5963-74. PMID:14609943
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