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PDBsum entry 3mpi
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Oxidoreductase
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PDB id
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3mpi
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References listed in PDB file
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Key reference
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Title
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Structural basis for promoting and preventing decarboxylation in glutaryl-Coenzyme a dehydrogenases.
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Authors
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S.Wischgoll,
U.Demmer,
E.Warkentin,
R.Günther,
M.Boll,
U.Ermler.
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Ref.
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Biochemistry, 2010,
49,
5350-5357.
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PubMed id
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Abstract
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Glutaryl-coenzyme A dehydrogenases (GDHs) involved in amino acid degradation
were thought to catalyze both the dehydrogenation and decarboxylation of
glutaryl-coenzyme A to crotonyl-coenzyme A and CO(2). Recently, a structurally
related but nondecarboxylating, glutaconyl-coenzyme A-forming GDH was
characterized in the obligately anaerobic bacteria Desulfococcus multivorans
(GDH(Des)) which conserves the free energy of decarboxylation by a Na(+)-pumping
glutaconyl-coenzyme A decarboxylase. To understand the distinct catalytic
behavior of the two GDH types on an atomic basis, we determined the crystal
structure of GDH(Des) with and without glutaconyl-coenzyme A bound at 2.05 and
2.1 A resolution, respectively. The decarboxylating and nondecarboxylating
capabilities are provided by complex structural changes around the glutaconyl
carboxylate group, the key factor being a Tyr --> Val exchange strictly
conserved between the two GDH types. As a result, the interaction between the
glutaconyl carboxylate and the guanidinium group of a conserved arginine is
stronger in GDH(Des) (short and planar bidentate hydrogen bond) than in the
decarboxylating human GDH (longer and monodentate hydrogen bond), which is
corroborated by molecular dynamics studies. The identified structural changes
prevent decarboxylation (i) by strengthening the C4-C5 bond of
glutaconyl-coenzyme A, (ii) by reducing the leaving group potential of CO(2),
and (iii) by increasing the distance between the C4 atom (negatively charged in
the dienolate transition state) and the adjacent glutamic acid.
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