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Title
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Crystal structure analysis and molecular model of a complex of citrate synthase with oxaloacetate and S-acetonyl-coenzyme A.
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Authors
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G.Wiegand,
S.Remington,
J.Deisenhofer,
R.Huber.
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Ref.
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J Mol Biol, 1984,
174,
205-219.
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PubMed id
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Abstract
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The crystal structure of the complex of pig heart citrate synthase and
oxaloacetate in the presence of the potent inhibitor S-acetonyl coenzyme A has
been determined at a nominal resolution of 2.9 A by Patterson search techniques
and refined by restrained crystallographic refinement. The complex crystallizes
in the presence of polyvinylpyrrolidone in space group P4(3)2(1)2 with a = 101.5
A and c = 224.6 A, with one dimeric molecule of molecular weight 100,000 in the
asymmetric unit. The crystallographic R factor is 0.194 for the 14,332 unique
reflections between 6.0 and 2.9 A resolution. The structures of two forms of
citrate synthase in the presence and absence of product molecules have been
determined recently and shown to differ in the relative arrangement of the large
and small domains ("closed" and "open" forms). The third crystal form described
here is also closed, but there is substantial rearrangement within the small
domain relative to either of the other crystal forms. We conclude that this is a
third structural state of the enzyme, and catalytic activity of the enzyme
depends on structural changes during the course of the reaction affecting domain
conformation also. The three structures are compared, and it is shown that the
large domain is considerably more rigid than the small domain. The conformation
of the small domain adapts to the ligand. The inhibitor, and the
"coenzyme-A-binding segment" of the enzyme are disordered. No electron density
is observed for the inhibitor, and only weak density for the coenzyme-A-binding
segment. Electron density for oxaloacetate is well defined. It binds in a very
similar manner to citrate.
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