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PDBsum entry 2p8c
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References listed in PDB file
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Key reference
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Title
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Prediction and assignment of function for a divergent n-Succinyl amino acid racemase.
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Authors
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L.Song,
C.Kalyanaraman,
A.A.Fedorov,
E.V.Fedorov,
M.E.Glasner,
S.Brown,
H.J.Imker,
P.C.Babbitt,
S.C.Almo,
M.P.Jacobson,
J.A.Gerlt.
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Ref.
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Nat Chem Biol, 2007,
3,
486-491.
[DOI no: ]
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PubMed id
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Abstract
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The protein databases contain many proteins with unknown function. A
computational approach for predicting ligand specificity that requires only the
sequence of the unknown protein would be valuable for directing experiment-based
assignment of function. We focused on a family of unknown proteins in the
mechanistically diverse enolase superfamily and used two approaches to assign
function: (i) enzymatic assays using libraries of potential substrates, and (ii)
in silico docking of the same libraries using a homology model based on the most
similar (35% sequence identity) characterized protein. The results matched
closely; an experimentally determined structure confirmed the predicted
structure of the substrate-liganded complex. We assigned the N-succinyl
arginine/lysine racemase function to the family, correcting the annotation
(L-Ala-D/L-Glu epimerase) based on the function of the most similar
characterized homolog. These studies establish that ligand docking to a homology
model can facilitate functional assignment of unknown proteins by restricting
the identities of the possible substrates that must be experimentally tested.
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Figure 2.
(a) AEE from B. subtilis with the L-Ala-L-Glu ligand as
determined by X-ray crystallography. (b) BC0371 with the
N-succinyl-L-arginine ligand as predicted by homology modeling
and docking. Catalytic residues are shown in tube
representation; ligands and critical binding site residues are
shown in ball-and-stick representation.
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Figure 3.
The homology-modeled active site is shown in cyan, and the
experimentally determined active site is shown in yellow. The
residues that determine substrate specificity are labeled.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Chem Biol
(2007,
3,
486-491)
copyright 2007.
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