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* Residue conservation analysis
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Enzyme class 1:
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Chains A, B:
E.C.2.5.1.58
- protein farnesyltransferase.
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Reaction:
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L-cysteinyl-[protein] + (2E,6E)-farnesyl diphosphate = S-(2E,6E)- farnesyl-L-cysteinyl-[protein] + diphosphate
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L-cysteinyl-[protein]
Bound ligand (Het Group name = )
matches with 62.50% similarity
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+
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(2E,6E)-farnesyl diphosphate
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=
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S-(2E,6E)- farnesyl-L-cysteinyl-[protein]
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+
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diphosphate
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Cofactor:
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Mg(2+); Zn(2+)
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Enzyme class 2:
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Chain A:
E.C.2.5.1.59
- protein geranylgeranyltransferase type I.
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Reaction:
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geranylgeranyl diphosphate + L-cysteinyl-[protein] = S-geranylgeranyl-L- cysteinyl-[protein] + diphosphate
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geranylgeranyl diphosphate
Bound ligand (Het Group name = )
matches with 51.72% similarity
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L-cysteinyl-[protein]
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=
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S-geranylgeranyl-L- cysteinyl-[protein]
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+
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diphosphate
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Cofactor:
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Zn(2+)
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Note, where more than one E.C. class is given (as above), each may
correspond to a different protein domain or, in the case of polyprotein
precursors, to a different mature protein.
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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DOI no:
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Biochemistry
45:9746-9755
(2006)
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PubMed id:
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Conversion of protein farnesyltransferase to a geranylgeranyltransferase.
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K.L.Terry,
P.J.Casey,
L.S.Beese.
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ABSTRACT
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Posttranslational modifications are essential for the proper function of a
number of proteins in the cell. One such modification, the covalent attachment
of a single isoprenoid lipid (prenylation), is carried out by the CaaX
prenyltransferases, protein farnesyltransferase (FTase) and protein
geranylgeranyltransferase type-I (GGTase-I). Substrate proteins of these two
enzymes are involved in a variety of cellular functions but are largely
associated with signal transduction. These modified proteins include members of
the Ras superfamily, heterotrimeric G-proteins, centromeric proteins, and a
number of proteins involved in nuclear integrity. Although FTase and GGTase-I
are highly homologous, they are quite selective for their substrates,
particularly for their isoprenoid diphosphate substrates, FPP and GGPP,
respectively. Here, we present both crystallographic and kinetic analyses of
mutants designed to explore this isoprenoid specificity and demonstrate that
this specificity is dependent upon two enzyme residues in the beta subunits of
the enzymes, W102beta and Y365beta in FTase (T49beta and F324beta, respectively,
in GGTase-I).
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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Y.Qiao,
J.Gao,
Y.Qiu,
L.Wu,
F.Guo,
K.K.Lo,
and
D.Li
(2011).
Design, synthesis, and characterization of piperazinedione-based dual protein inhibitors for both farnesyltransferase and geranylgeranyltransferase-I.
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Eur J Med Chem,
46,
2264-2273.
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U.T.Nguyen,
R.S.Goody,
and
K.Alexandrov
(2010).
Understanding and exploiting protein prenyltransferases.
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Chembiochem,
11,
1194-1201.
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J.L.Hougland,
C.L.Lamphear,
S.A.Scott,
R.A.Gibbs,
and
C.A.Fierke
(2009).
Context-dependent substrate recognition by protein farnesyltransferase.
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Biochemistry,
48,
1691-1701.
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M.A.Hast,
S.Fletcher,
C.G.Cummings,
E.E.Pusateri,
M.A.Blaskovich,
K.Rivas,
M.H.Gelb,
W.C.Van Voorhis,
S.M.Sebti,
A.D.Hamilton,
and
L.S.Beese
(2009).
Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase.
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Chem Biol,
16,
181-192.
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PDB codes:
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K.Yokoyama,
J.R.Gillespie,
W.C.Van Voorhis,
F.S.Buckner,
and
M.H.Gelb
(2008).
Protein geranylgeranyltransferase-I of Trypanosoma cruzi.
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Mol Biochem Parasitol,
157,
32-43.
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M.A.Hast,
and
L.S.Beese
(2008).
Structure of Protein Geranylgeranyltransferase-I from the Human Pathogen Candida albicans Complexed with a Lipid Substrate.
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J Biol Chem,
283,
31933-31940.
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PDB code:
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Z.Guo,
Y.W.Wu,
D.Das,
C.Delon,
J.Cramer,
S.Yu,
S.Thuns,
N.Lupilova,
H.Waldmann,
L.Brunsveld,
R.S.Goody,
K.Alexandrov,
and
W.Blankenfeldt
(2008).
Structures of RabGGTase-substrate/product complexes provide insights into the evolution of protein prenylation.
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EMBO J,
27,
2444-2456.
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
