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PDBsum entry 1leh
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Oxidoreductase
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PDB id
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1leh
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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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A role for quaternary structure in the substrate specificity of leucine dehydrogenase.
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Authors
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P.J.Baker,
A.P.Turnbull,
S.E.Sedelnikova,
T.J.Stillman,
D.W.Rice.
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Ref.
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Structure, 1995,
3,
693-705.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Glutamate, phenylalanine and leucine dehydrogenases catalyze the
NAD(P)(+)-linked oxidative deamination of L-amino acids to the corresponding
2-oxoacids, and sequence homology between these enzymes clearly indicates the
existence of an enzyme superfamily related by divergent evolution. We have
undertaken structural studies on a number of members of this family in order to
investigate the molecular basis of their differential amino acid specificity.
RESULTS: We have solved the X-ray structure of the leucine dehydrogenase from
Bacillus sphaericus to a resolution of 2.2 A. Each subunit of this octameric
enzyme contains 364 amino acids and folds into two domains, separated by a deep
cleft. The nicotinamide ring of the NAD+ cofactor binds deep in this cleft,
which is thought to close during the hydride transfer step of the catalytic
cycle. CONCLUSIONS: Comparison of the structure of leucine dehydrogenase with a
hexameric glutamate dehydrogenase has shown that these two enzymes share a
related fold and possess a similar catalytic chemistry. A mechanism for the
basis of the differential amino acid specificity between these enzymes involves
point mutations in the amino acid side-chain specificity pocket and subtle
changes in the shape of this pocket caused by the differences in quaternary
structure.
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Figure 2.
Figure 2. Stereo diagrams of a single subunit of LeuDH. The
organization of the subunit into two domains, separated by a
deep cleft, can be seen. In this view the fourfold axis of the
LeuDH octamer runs vertically. (a) Schematic representation with
the strands and helices numbered. (b) Cα trace with every
tenth residue indicated by a black dot. Figure 2. Stereo
diagrams of a single subunit of LeuDH. The organization of the
subunit into two domains, separated by a deep cleft, can be
seen. In this view the fourfold axis of the LeuDH octamer runs
vertically. (a) Schematic representation with the strands and
helices numbered. (b) Cα trace with every tenth residue
indicated by a black dot. (Figure prepared using MOLSCRIPT
[[3]41].)
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Figure 4.
Figure 4. Stereo ribbon diagram illustrating the interactions
around the fourfold axis in LeuDH. Two monomers are shown (red
and green), viewed down the non-crystallographic twofold axis
which relates pairs of dimers, with the fourfold axis vertical.
Figure 4. Stereo ribbon diagram illustrating the interactions
around the fourfold axis in LeuDH. Two monomers are shown (red
and green), viewed down the non-crystallographic twofold axis
which relates pairs of dimers, with the fourfold axis vertical.
(Figure prepared using FRODO [[3]38].)
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The above figures are
reprinted
by permission from Cell Press:
Structure
(1995,
3,
693-705)
copyright 1995.
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Secondary reference #1
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Title
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Crystallization and quaternary structure analysis of the NAD(+)-Dependent leucine dehydrogenase from bacillus sphaericus.
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Authors
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A.P.Turnbull,
S.R.Ashford,
P.J.Baker,
D.W.Rice,
F.H.Rodgers,
T.J.Stillman,
R.L.Hanson.
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Ref.
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J Mol Biol, 1994,
236,
663-665.
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PubMed id
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Secondary reference #2
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Title
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Evolution of substrate diversity in the superfamily of amino acid dehydrogenases. Prospects for rational chiral synthesis.
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Authors
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K.L.Britton,
P.J.Baker,
P.C.Engel,
D.W.Rice,
T.J.Stillman.
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Ref.
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J Mol Biol, 1993,
234,
938-945.
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PubMed id
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