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PDBsum entry 9ldb
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Oxidoreductase(choh(d)-NAD+(a))
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PDB id
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9ldb
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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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Design and synthesis of new enzymes based on the lactate dehydrogenase framework.
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Authors
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C.R.Dunn,
H.M.Wilks,
D.J.Halsall,
T.Atkinson,
A.R.Clarke,
H.Muirhead,
J.J.Holbrook.
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Ref.
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Philos Trans R Soc Lond B Biol Sci, 1991,
332,
177-184.
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PubMed id
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Abstract
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Analysis of the mechanism and structure of lactate dehydrogenases is summarized
in a map of the catalytic pathway. Chemical probes, single tryptophan residues
inserted at specific sites and a crystal structure reveal slow movements of the
protein framework that discriminate between closely related small substrates.
Only small and correctly charged substrates allow the protein to engulf the
substrate in an internal vacuole that is isolated from solvent protons, in which
water is frozen and hydride transfer is rapid. The closed vacuole is very
sensitive to the size and charge of the substrate and provides discrimination
between small substrates that otherwise have too few functional groups to be
distinguished at a solvated protein surface. This model was tested against its
ability to successfully predict the design and synthesis of new enzymes such as
L-hydroxyisocaproate dehydrogenase and fully active malate dehydrogenase.
Solvent friction limits the rate of forming the vacuole and thus the maximum
rate of catalysis.
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