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PDBsum entry 1n4q
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Contents |
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(+ 0 more)
314 a.a.
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(+ 0 more)
346 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure of mammalian protein geranylgeranyltransferase type-I.
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Authors
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J.S.Taylor,
T.S.Reid,
K.L.Terry,
P.J.Casey,
L.S.Beese.
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Ref.
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Embo J, 2003,
22,
5963-5974.
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PubMed id
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Abstract
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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.
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