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PDBsum entry 1qb8
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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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Crystal structures of adenine phosphoribosyltransferase from leishmania donovani.
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Authors
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C.L.Phillips,
B.Ullman,
R.G.Brennan,
C.P.Hill.
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Ref.
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EMBO J, 1999,
18,
3533-3545.
[DOI no: ]
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PubMed id
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Abstract
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The enzyme adenine phosphoribosyltransferase (APRT) functions to salvage adenine
by converting it to adenosine-5-monophosphate (AMP). APRT deficiency in humans
is a well characterized inborn error of metabolism, and APRT may contribute to
the indispensable nutritional role of purine salvage in protozoan parasites, all
of which lack de novo purine biosynthesis. We determined crystal structures for
APRT from Leishmania donovani in complex with the substrate adenine, the product
AMP, and sulfate and citrate ions that appear to mimic the binding of phosphate
moieties. Overall, these structures are very similar to each other, although the
adenine and AMP complexes show different patterns of hydrogen-bonding to the
base, and the active site pocket opens slightly to accommodate the larger AMP
ligand. Whereas AMP adopts a single conformation, adenine binds in two mutually
exclusive orientations: one orientation providing adenine-specific hydrogen
bonds and the other apparently positioning adenine for the enzymatic reaction.
The core of APRT is similar to that of other phosphoribosyltransferases,
although the adenine-binding domain is quite different. A C-terminal extension,
unique to Leishmania APRTs, extends an extensive dimer interface by wrapping
around the partner molecule. The active site involves residues from both
subunits of the dimer, indicating that dimerization is essential for catalysis.
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Figure 7.
Figure 7 Schematic representation of contacts to AMP. Hydrogen
bonds and metal–ligand contacts are indicated with a dotted
line and defined as for Figure 8.
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Figure 10.
Figure 10 Superposition of APRT active site structures.
AMP–APRT red; apo-AS–APRT green; Ade–APRT A orientation
light blue; Ade–APRT B orientation dark blue.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(1999,
18,
3533-3545)
copyright 1999.
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