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PDBsum entry 1ivh
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Oxidoreductase
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PDB id
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1ivh
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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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Structure of human isovaleryl-Coa dehydrogenase at 2.6 a resolution: structural basis for substrate specificity,.
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Authors
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K.A.Tiffany,
D.L.Roberts,
M.Wang,
R.Paschke,
A.W.Mohsen,
J.Vockley,
J.J.Kim.
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Ref.
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Biochemistry, 1997,
36,
8455-8464.
[DOI no: ]
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PubMed id
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Abstract
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Isovaleryl-CoA dehydrogenase (IVD) belongs to an important flavoprotein family
of acyl-CoA dehydrogenases that catalyze the alpha,beta-dehydrogenation of their
various thioester substrates. Although enzymes from this family share similar
sequences, catalytic mechanisms, and structural properties, the position of the
catalytic base in the primary sequence is not conserved. E376 has been confirmed
to be the catalytic base in medium-chain (MCAD) and short-chain acyl-CoA
dehydrogenases and is conserved in all members of the acyl-CoA dehydrogenase
family except for IVD and long-chain acyl-CoA dehydrogenase. To understand this
dichotomy and to gain a better understanding of the factors important in
determining substrate specificity in this enzyme family, the three-dimensional
structure of human IVD has been determined. Human IVD expressed in Escherichia
coli crystallizes in the orthorhombic space group P212121 with unit cell
parameters a = 94.0 A, b = 97.7 A, and c = 181.7 A. The structure of IVD was
solved at 2.6 A resolution by the molecular replacement method and was refined
to an R-factor of 20.7% with an Rfree of 28.8%. The overall polypeptide fold of
IVD is similar to that of other members of this family for which structural data
are available. The tightly bound ligand found in the active site of the
structure of IVD is consistent with that of CoA persulfide. The identity of the
catalytic base was confirmed to be E254, in agreement with previous molecular
modeling and mutagenesis studies. The location of the catalytic residue together
with a glycine at position 374, which is a tyrosine in all other members of the
acyl-CoA dehydrogenase family, is important for conferring branched-chain
substrate specificity to IVD.
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