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PDBsum entry 1f0y
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Oxidoreductase
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PDB id
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1f0y
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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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Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of l-3-Hydroxyacyl-Coa dehydrogenase.
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Authors
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J.J.Barycki,
L.K.O'Brien,
A.W.Strauss,
L.J.Banaszak.
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Ref.
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J Biol Chem, 2000,
275,
27186-27196.
[DOI no: ]
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PubMed id
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Abstract
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l-3-Hydroxyacyl-CoA dehydrogenase reversibly catalyzes the conversion of
l-3-hydroxyacyl-CoA to 3-ketoacyl-CoA concomitant with the reduction of NAD(+)
to NADH as part of the beta-oxidation spiral. In this report, crystal structures
have been solved for the apoenzyme, binary complexes of the enzyme with reduced
cofactor or 3-hydroxybutyryl-CoA substrate, and an abortive ternary complex of
the enzyme with NAD(+) and acetoacetyl-CoA. The models illustrate positioning of
cofactor and substrate within the active site of the enzyme. Comparison of these
structures with the previous model of the enzyme-NAD(+) complex reveals that
although significant shifting of the NAD(+)-binding domain relative to the
C-terminal domain occurs in the ternary and substrate-bound complexes, there are
few differences between the apoenzyme and cofactor-bound complexes. Analysis of
these models clarifies the role of key amino acids implicated in catalysis and
highlights additional critical residues. Furthermore, a novel charge transfer
complex has been identified in the course of abortive ternary complex formation,
and its characterization provides additional insight into aspects of the
catalytic mechanism of l-3-hydroxyacyl-CoA dehydrogenase.
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Figure 2.
Fig. 2. L-3-Hydroxyacyl-CoA dehydrogenase complexed with
the substrate, 3-hydroxybutyryl-CoA. The ribbon diagram depicts
the two-domain structure of an HAD subunit, with the first 200
amino acids comprising the NAD +-binding domain and the
remaining residues comprising the C-terminal domain.
3-Hydroxybutyryl-CoA, shown in ball and stick representation,
binds within the cleft between these two domains. The adenine
moiety of coenzyme A is positioned adjacent to the
helix-turn-helix tail (  2- 3) of the
NAD^+-binding domain, and the acyl chain is within the enzyme
active site.
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Figure 4.
Fig. 4. Schematic of the 3-hydroxybutyryl-CoA-binding
site. Hydrogen bonds involved in binding of the substrate,
3-hydroxybutyryl-CoA, to the apoenzyme are represented as dashed
lines, with residues of the opposing subunit of the dimer
indicated with an asterisk.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2000,
275,
27186-27196)
copyright 2000.
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Secondary reference #1
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Title
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Biochemical characterization and crystal structure determination of human heart short chain l-3-Hydroxyacyl-Coa dehydrogenase provide insights into catalytic mechanism.
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Authors
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J.J.Barycki,
L.K.O'Brien,
J.M.Bratt,
R.Zhang,
R.Sanishvili,
A.W.Strauss,
L.J.Banaszak.
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Ref.
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Biochemistry, 1999,
38,
5786-5798.
[DOI no: ]
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PubMed id
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