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PDBsum entry 2i2c
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References listed in PDB file
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Key reference
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Title
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Nad kinases use substrate-Assisted catalysis for specific recognition of NAD.
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Authors
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G.Poncet-Montange,
L.Assairi,
S.Arold,
S.Pochet,
G.Labesse.
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Ref.
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J Biol Chem, 2007,
282,
33925-33934.
[DOI no: ]
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PubMed id
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Abstract
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Here we describe the crystal structures of the NAD kinase (LmNADK1) from
Listeria monocytogenes in complex with its substrate NAD, its product NADP, or
two synthesized NAD mimics. We identified one of the NAD mimics, di-adenosine
diphosphate, as a new substrate for LmNADK1, whereas we showed that the closely
related compound di-5'-thioadenosine is a novel non-natural inhibitor for this
enzyme. These structures suggest a mechanism involving substrate-assisted
catalysis. Indeed, sequence/structure comparison and directed mutagenesis have
previously shown that NAD kinases (NADKs) and the distantly related
6-phosphofructokinases share the same catalytically important GGDGT motif.
However, in this study we have shown that these enzymes use the central
aspartate of this motif differently. Although this acidic residue chelates the
catalytic Mg(2+) ion in 6-phosphofructokinases, it activates the
phospho-acceptor (NAD) in NADKs. Sequence/structure comparisons suggest that the
role of this aspartate would be conserved in NADKs and the related sphingosine
and diacylglycerol kinases.
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Figure 1.
Schematic reaction and chemical structures of nucleotides
described in this study.A, schematic reaction of the NADKs. B,
dinucleotides linked by a diphosphate group and representation
of adenine and nicotinamide moiety. C, dinucleotide linked by a
disulfide bridge (DTA) and its protected form (TAA).
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Figure 3.
Stereo view of the superposed N-terminal domains of NADKs and
PFKs. The N termini of LmNADK1 and E. coli PFK were superposed
using the program ViTO (33). The picture was generated by the
program PYMOL. Gray and black schematics and wireframes
represent E. coli PFK/ADP/FBP/Mg^2+ and LmNADK1/NAD,
respectively.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
33925-33934)
copyright 2007.
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