1n4q
From Proteopedia
(New page: 200px<br /><applet load="1n4q" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n4q, resolution 2.40Å" /> '''Protein Geranylgeran...) |
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| - | [[Image:1n4q.gif|left|200px]]<br /><applet load="1n4q" size=" | + | [[Image:1n4q.gif|left|200px]]<br /><applet load="1n4q" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1n4q, resolution 2.40Å" /> | caption="1n4q, resolution 2.40Å" /> | ||
'''Protein Geranylgeranyltransferase type-I Complexed with a GGPP Analog and a KKKSKTKCVIL Peptide'''<br /> | '''Protein Geranylgeranyltransferase type-I Complexed with a GGPP Analog and a KKKSKTKCVIL Peptide'''<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== | ||
| - | 1N4Q 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, TTH and MGM as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1N4Q 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=TTH:'>TTH</scene> and <scene name='pdbligand=MGM:'>MGM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N4Q 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: MGM]] | [[Category: MGM]] | ||
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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 14:02:13 2008'' |
Revision as of 12:02, 21 February 2008
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Protein Geranylgeranyltransferase type-I Complexed with a GGPP Analog and a KKKSKTKCVIL Peptide
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
1N4Q is a Protein complex structure of sequences from Rattus norvegicus with , , and 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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