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Title
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The presence of a histidine-aspartic acid pair in the active site of 2-hydroxyacid dehydrogenases. X-ray refinement of cytoplasmic malate dehydrogenase.
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Authors
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J.J.Birktoft,
L.J.Banaszak.
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Ref.
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J Biol Chem, 1983,
258,
472-482.
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PubMed id
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Abstract
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The structure of cytoplasmic malate dehydrogenase has been partially refined by
crystallographic least squares methods. Using x-ray phases based on the refined
coordinates, analysis of the resultant electron density maps has led to a new
model of cytoplasmic malate dehydrogenase and a tentative "x-ray sequence." The
two crystallographically independent subunits comprising the dimeric enzyme are
nearly identical in structure and are related to each other by roughly 2-fold
rotational symmetry. The best fit of the molecular structure of cytoplasmic
malate dehydrogenase to that of lactate dehydrogenase has been obtained by least
squares methods. The active sites of these two enzymes contain similarly
oriented His-Asp pairs linked by a hydrogen bond which may function as a proton
relay system during catalysis. This pair could also provide an explanation for
the relatively stronger binding by cytoplasmic malate dehydrogenase and lactate
dehydrogenase of NADH versus NAD. Similar His-Asp pairs have been observed in
the serine proteases, thermolysin, and phospholipase A2, and the His-Asp pair
may play a similar functional role in all of these enzymes.
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