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PDBsum entry 1i10
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Oxidoreductase
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PDB id
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1i10
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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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Structural basis for altered activity of m- And h-Isozyme forms of human lactate dehydrogenase.
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Authors
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J.A.Read,
V.J.Winter,
C.M.Eszes,
R.B.Sessions,
R.L.Brady.
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Ref.
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Proteins, 2001,
43,
175-185.
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PubMed id
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Abstract
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Lactate dehydrogenase (LDH) interconverts pyruvate and lactate with concomitant
interconversion of NADH and NAD(+). Although crystal structures of a variety of
LDH have previously been described, a notable absence has been any of the three
known human forms of this glycolytic enzyme. We have now determined the crystal
structures of two isoforms of human LDH-the M form, predominantly found in
muscle; and the H form, found mainly in cardiac muscle. Both structures have
been crystallized as ternary complexes in the presence of the NADH cofactor and
oxamate, a substrate-like inhibitor. Although each of these isoforms has
different kinetic properties, the domain structure, subunit association, and
active-site regions are indistinguishable between the two structures. The pK(a)
that governs the K(M) for pyruvate for the two isozymes is found to differ by
about 0.94 pH units, consistent with variation in pK(a) of the active-site
histidine. The close similarity of these crystal structures suggests the
distinctive activity of these enzyme isoforms is likely to result directly from
variation of charged surface residues peripheral to the active site, a
hypothesis supported by electrostatic calculations based on each structure.
Proteins 2001;43:175-185.
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