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PDBsum entry 3rtc
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References listed in PDB file
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Key reference
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Title
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Identification of unknown protein function using metabolite cocktail screening.
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Authors
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I.A.Shumilin,
M.Cymborowski,
O.Chertihin,
K.N.Jha,
J.C.Herr,
S.A.Lesley,
A.Joachimiak,
W.Minor.
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Ref.
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Structure, 2012,
20,
1715-1725.
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Proteins of unknown function comprise a significant fraction of sequenced
genomes. Defining the roles of these proteins is vital to understanding cellular
processes. Here, we describe a method to determine a protein function based on
the identification of its natural ligand(s) by the crystallographic screening of
the binding of a metabolite library, followed by a focused search in the
metabolic space. The method was applied to two protein families with unknown
function, PF01256 and YjeF_N. The PF01256 proteins, represented by YxkO from
Bacillus subtilis and the C-terminal domain of Tm0922 from Thermotoga maritima,
were shown to catalyze ADP/ATP-dependent NAD(P)H-hydrate dehydratation, a
previously described orphan activity. The YjeF_N proteins, represented by mouse
apolipoprotein A-I binding protein and the N-terminal domain of Tm0922, were
found to interact with an adenosine diphosphoribose-related substrate and likely
serve as ADP-ribosyltransferases. Crystallographic screening of metabolites
serves as an efficient tool in functional analyses of uncharacterized proteins.
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