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PDBsum entry 1qap
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Glycosyltransferase
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PDB id
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1qap
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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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A new function for a common fold: the crystal structure of quinolinic acid phosphoribosyltransferase.
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Authors
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J.C.Eads,
D.Ozturk,
T.B.Wexler,
C.Grubmeyer,
J.C.Sacchettini.
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Ref.
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Structure, 1997,
5,
47-58.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Quinolinic acid (QA) is a neurotoxin and has been shown to be
present at high levels in the central nervous system of patients with certain
diseases, such as AIDS and meningitis. The enzyme quinolinic acid
phosphoribosyltransferase (QAPRTase) provides the only route for QA metabolism
and is also an essential step in de novo NAD biosynthesis. QAPRTase catalyzes
the synthesis of nicotinic acid mononucleotide (NAMN) from QA and
5-phosphoribosyl-1-pyrophosphate (PRPP). The structures of several
phosphoribosyltransferases (PRTases) have been reported, and all have shown a
similar fold of a five-strandard beta sheet surrounded by four alpha helices. A
conserved sequence motif of 13 residues is common to these 'type I' PRTases but
is not observed in the QAPRTase sequence, suggestive of a different fold for
this enzyme. RESULTS: The crystal structure of QAPRTase from Salmonella
typhimurium has been determined with bound QA to 2.8 A resolution, and with
bound NAMN to 3.0 A resolution. Most significantly, the enzyme shows a
completely novel fold for a PRTase enzyme comprising a two-domain structure: a
mixed alpha/beta N-terminal domain and an alpha/beta barrel-like domain
containing seven beta strands. The active site is located at the C-terminal ends
of the beta strands of the alpha/beta barrel, and is bordered by the N-terminal
domain of the second subunit of the dimer. The active site is largely composed
of a number of conserved charged residues that appear to be important for
substrate binding and catalysis. CONCLUSIONS: The seven-stranded
alpha/beta-barrel domain of QAPRTase is very similar in structure to the
eight-stranded alpha/beta-barrel enzymes. The structure shows a
phosphate-binding site that appears to be conserved among many alpha/beta-barrel
enzymes including indole-3-glycerol phosphate synthase and flavocytochrome b2.
The new fold observed here demonstrates that the PRTase enzymes have evolved
their similar chemistry from at least two completely different protein
architectures.
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Figure 9.
Figure 9. Overlay of the phosphate-binding site regions of
QAPRTase (in blue), flavocytochrome b2 (in magenta) and
indole-3-glycerol phosphate synthase (in green). The bound NAMN
is shown in stick form with atom coloring as in Figure 6.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1997,
5,
47-58)
copyright 1997.
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