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PDBsum entry 3elh
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References listed in PDB file
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Key reference
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Title
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Dissecting the unique nucleotide specificity of mimivirus nucleoside diphosphate kinase.
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Authors
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S.Jeudy,
A.Lartigue,
J.M.Claverie,
C.Abergel.
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Ref.
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J Virol, 2009,
83,
7142-7150.
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PubMed id
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Abstract
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The analysis of the Acanthamoeba polyphaga mimivirus genome revealed the first
virus-encoded nucleoside diphosphate kinase (NDK), an enzyme that is central to
the synthesis of RNA and DNA, ubiquitous in cellular organisms, and well
conserved among the three domains of life. In contrast with the broad
specificity of cellular NDKs for all types of ribo- and deoxyribonucleotides,
the mimivirus enzyme exhibits a strongly preferential affinity for
deoxypyrimidines. In order to elucidate the molecular basis of this unique
substrate specificity, we determined the three-dimensional (3D) structure of the
Acanthamoeba polyphaga mimivirus NDK alone and in complex with various
nucleotides. As predicted from a sequence comparison with cellular NDKs, the 3D
structure of the mimivirus enzyme exhibits a shorter Kpn loop, previously
recognized as a main feature of the NDK active site. The structure of the viral
enzyme in complex with various nucleotides also pinpointed two residue changes,
both located near the active site and specific to the viral NDK, which could
explain its stronger affinity for deoxynucleotides and pyrimidine nucleotides.
The role of these residues was explored by building a set of viral NDK variants,
assaying their enzymatic activities, and determining their 3D structures in
complex with various nucleotides. A total of 26 crystallographic structures were
determined at resolutions ranging from 2.8 A to 1.5 A. Our results suggest that
the mimivirus enzyme progressively evolved from an ancestral NDK under the
constraints of optimizing its efficiency for the replication of an AT-rich (73%)
viral genome in a thymidine-limited host environment.
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