Open AccessStructure of L-3-hydroxyacyl-coenzyme A dehydrogenase: preliminary chain tracing at 2.8-A resolution.
Author(s) -
Jens J. Birktoft,
Hazel M. Holden,
R. Hamlin,
N.-H. Xuong,
Leonard J. Banaszak
Publication year - 1987
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.84.23.8262
Subject(s) - cofactor , nad+ kinase , dehydrogenase , oxidoreductase , stereochemistry , dimer , chemistry , binding site , protein subunit , biochemistry , enzyme , protein structure , crystallography , gene , organic chemistry
The conformation of L-3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.35) has been derived from electron-density maps calculated at 2.8-A resolution with phases obtained from two heavy-atom derivatives and the bound coenzyme, NAD. Like other dehydrogenases, 3-hydroxyacyl-CoA dehydrogenase is a double-domain structure, but the bilobal nature of this enzyme is more pronounced than has been previously observed. The amino-terminal domain, which comprises approximately the first 200 residues, is responsible for binding the NAD cofactor and displays considerable structural homology with the dinucleotide binding domains observed in other NAD-, NADP-, and FAD-dependent enzymes. The carboxyl-terminal domain, comprising the remaining 107 residues, appears to be all alpha-helical and bears little homology to other known dehydrogenases. The subunit-subunit interface in the 3-hydroxyacyl-CoA dehydrogenase dimer is formed almost exclusively by residues in the smaller helical domain. A difference map between the apo and holo forms of the crystalline enzyme has been interpreted in terms of the NAD molecule being bound in a typically extended conformation. The location of the coenzyme binding site, along with the structural homology to other dehydrogenases, makes it possible to speculate about the location of the binding site for the fatty acyl-CoA substrate.