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PDBsum entry 3l2b
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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 the cbs and drtgg domains of the regulatory region of clostridiumperfringens pyrophosphatase complexed with the inhibitor, Amp, And activator, Diadenosine tetraphosphate.
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Authors
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H.Tuominen,
A.Salminen,
E.Oksanen,
J.Jämsen,
O.Heikkilä,
L.Lehtiö,
N.N.Magretova,
A.Goldman,
A.A.Baykov,
R.Lahti.
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Ref.
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J Mol Biol, 2010,
398,
400-413.
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PubMed id
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Abstract
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Nucleotide-binding cystathionine beta-synthase (CBS) domains serve as regulatory
units in numerous proteins distributed in all kingdoms of life. However, the
underlying regulatory mechanisms remain to be established. Recently, we
described a subfamily of CBS domain-containing pyrophosphatases (PPases) within
family II PPases. Here, we express a novel CBS-PPase from Clostridium
perfringens (CPE2055) and show that the enzyme is inhibited by AMP and activated
by a novel effector, diadenosine 5',5-P1,P4-tetraphosphate (AP(4)A). The
structures of the AMP and AP(4)A complexes of the regulatory region of C.
perfringens PPase (cpCBS), comprising a pair of CBS domains interlinked by a
DRTGG domain, were determined at 2.3 A resolution using X-ray crystallography.
The structures obtained are the first structures of a DRTGG domain as part of a
larger protein structure. The AMP complex contains two AMP molecules per cpCBS
dimer, each bound to a single monomer, whereas in the activator-bound complex,
one AP(4)A molecule bridges two monomers. In the nucleotide-bound structures,
activator binding induces significant opening of the CBS domain interface,
compared with the inhibitor complex. These results provide structural insight
into the mechanism of CBS-PPase regulation by nucleotides.
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