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PDBsum entry 1kpe
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Protein kinase inhibitor
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PDB id
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1kpe
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Contents |
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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-Based analysis of catalysis and substrate definition in the hit protein family.
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Authors
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C.D.Lima,
M.G.Klein,
W.A.Hendrickson.
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Ref.
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Science, 1997,
278,
286-290.
[DOI no: ]
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PubMed id
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Abstract
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The histidine triad (HIT) protein family is among the most ubiquitous and highly
conserved in nature, but a biological activity has not yet been identified for
any member of the HIT family. Fragile histidine triad protein (FHIT) and protein
kinase C interacting protein (PKCI) were used in a structure-based approach to
elucidate characteristics of in vivo ligands and reactions. Crystallographic
structures of apo, substrate analog, pentacovalent transition-state analog, and
product states of both enzymes reveal a catalytic mechanism and define substrate
characteristics required for catalysis, thus unifying the HIT family as
nucleotidyl hydrolases, transferases, or both. The approach described here may
be useful in identifying structure-function relations between protein families
identified through genomics.
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Figure 2.
Fig. 2. Stereo views of PKCI in (A) apo, (B) AMP-CP substrate
analog, (C) adenosine-tungstate transition-state^ analog, and
(D) AMP product-bound forms. The region shown was selected to
highlight interactions between the ligand and^ protein residues
surrounding one of the two equivalent ligand-binding sites in
the HIT homodimer. A subset of residues is shown superimposed^
on the C  backbone
cardinal spline of each respective structure. Hydrogen bonds are
denoted by dotted lines. The tryptophan shown is in the
COOH-terminal tail of the other protomer. Figure generated^ with
Setor (15).
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Figure 3.
Fig. 3. Schematic diagram of FHIT in (A) apo, (B) AMP-CP
substrate analog, (C) adenosine-tungstate transition-state^
analog, and (D) adenosine-sulfate product complexed forms. As in
Fig. 2, hydrogen-bonding interactions are depicted by dotted^
lines. A subset of residues is shown superimposed on the C backbone^
cardinal spline of each respective structure.
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The above figures are
reprinted
by permission from the AAAs:
Science
(1997,
278,
286-290)
copyright 1997.
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Secondary reference #1
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Title
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Three-Dimensional structure of human protein kinase c interacting protein 1, A member of the hit family of proteins.
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Authors
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C.D.Lima,
M.G.Klein,
I.B.Weinstein,
W.A.Hendrickson.
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Ref.
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Proc Natl Acad Sci U S A, 1996,
93,
5357-5362.
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PubMed id
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