Structure of L-3-hydroxyacyl-coenzyme A dehydrogenase: preliminary chain tracing at 2. 8-Angstrom resolution

Journal Article · Tue Dec 01 04:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.23.8262· OSTI ID:6464910

Birktoft, J J; Holden, H M; Hamlin, R; Xuong, N H; Banaszak, L J

The conformation of L-3-hydroxyacyl-CoA dehydrogenase has been derived from electron-density maps calculated at 2.8-Angstrom 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 ..cap 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.

• Research Organization: Washington State Univ. School of Medicine, St. Louis, MO (USA)
• OSTI ID: 6464910
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:23; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550602* -- Medicine-- External Radiation in Diagnostics-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
COENZYMES
COHERENT SCATTERING
DIFFRACTION
ENZYMES
HEMIACETAL DEHYDROGENASES
MOLECULAR STRUCTURE
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDATION
OXIDOREDUCTASES
SCATTERING
STEREOCHEMISTRY
X-RAY DIFFRACTION