• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Dec 1987; 84(23): 8262–8266.
PMCID: PMC299522

Structure of L-3-hydroxyacyl-coenzyme A dehydrogenase: preliminary chain tracing at 2.8-A resolution.

Abstract

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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • WAKIL SJ, GREEN DE, MII S, MAHLER HR. Studies on the fatty acid oxidizing system of animal tissues. VI. beta-Hydroxyacyl coenzyme A dehydrogenase. J Biol Chem. 1954 Apr;207(2):631–638. [PubMed]
  • Noyes BE, Bradshaw RA. L-3-hydroxyacyl coenzyme A dehydrogenase from pig heart muscle. I. Purification and properties. J Biol Chem. 1973 May 10;248(9):3052–3059. [PubMed]
  • Noyes BE, Glatthaar BE, Garavelli JS, Bradshaw RA. Structural and functional similarities between mitochondrial malate dehydrogenase and L-3-hydroxyacyl CoA dehydrogenase. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1334–1338. [PMC free article] [PubMed]
  • Ozasa H, Furuta S, Miyazawa S, Osumi T, Hashimoto T, Mori M, Miura S, Tatibana M. Biosynthesis of enzymes of rat-liver mitochondrial beta-oxidation. Eur J Biochem. 1984 Nov 2;144(3):453–458. [PubMed]
  • Noyes BE, Bradshaw RA. L-3-hydroxyacyl coenzyme A dehydrogenase from pig heart muscle. II. Subunit structure. J Biol Chem. 1973 May 10;248(9):3061–3066. [PubMed]
  • Bitar KG, Perez-Aranda A, Bradshaw RA. Amino acid sequence of L-3-hydroxyacyl CoA dehydrogenase from pig heart muscle. FEBS Lett. 1980 Jul 28;116(2):196–198. [PubMed]
  • Weininger MS, Banaszak LJ. Mitochondrial malate dehydrogenase. Crystallographic properties of the pig heart enzyme. J Mol Biol. 1978 Mar 5;119(3):443–449. [PubMed]
  • Holden HM, Banaszak LJ. L-3-hydroxyacyl coenzyme A dehydrogenase. The location of NAD binding sites and the bilobal subunit structure. J Biol Chem. 1983 Feb 25;258(4):2383–2389. [PubMed]
  • Glatthaar BE, Barbarash GR, Noyes BE, Banaszak LJ, Bradshaw RA. The preparation of the cytoplasmic and mitochondrial forms of malate dehydrogenase and aspartate aminotransferase from pig heart by a single procedure. Anal Biochem. 1974 Feb;57(2):432–451. [PubMed]
  • Hamlin R. Multiwire area X-ray diffractometers. Methods Enzymol. 1985;114:416–452. [PubMed]
  • Howard AJ, Nielsen C, Xuong NH. Software for a diffractometer with multiwire area detector. Methods Enzymol. 1985;114:452–472. [PubMed]
  • Parks EH, Ernst SR, Hamlin R, Xuong NH, Hackert ML. Structure determination of histidine decarboxylase from Lactobacillus 30a at 3.0 A resolution. J Mol Biol. 1985 Apr 5;182(3):455–465. [PubMed]
  • Sheriff S, Herriott JR. Structure of ferredoxin-NADP oxidoreductase and the location on the NADP binding site. Results at 3-7 A resolution. J Mol Biol. 1981 Jan 15;145(2):441–451. [PubMed]
  • Wang BC. Resolution of phase ambiguity in macromolecular crystallography. Methods Enzymol. 1985;115:90–112. [PubMed]
  • Huber R, Bennett WS., Jr Functional significance of flexibility in proteins. Biopolymers. 1983 Jan;22(1):261–279. [PubMed]
  • Moras D, Olsen KW, Sabesan MN, Buehner M, Ford GC, Rossmann MG. Studies of asymmetry in the three-dimensional structure of lobster D-glyceraldehyde-3-phosphate dehydrogenase. J Biol Chem. 1975 Dec 10;250(23):9137–9162. [PubMed]
  • Schulz GE, Schirmer RH, Sachsenheimer W, Pai EF. The structure of the flavoenzyme glutathione reductase. Nature. 1978 May 11;273(5658):120–124. [PubMed]
  • Birktoft JJ, Banaszak LJ. The presence of a histidine-aspartic acid pair in the active site of 2-hydroxyacid dehydrogenases. X-ray refinement of cytoplasmic malate dehydrogenase. J Biol Chem. 1983 Jan 10;258(1):472–482. [PubMed]
  • Wiegand G, Remington S, Deisenhofer J, Huber R. Crystal structure analysis and molecular model of a complex of citrate synthase with oxaloacetate and S-acetonyl-coenzyme A. J Mol Biol. 1984 Mar 25;174(1):205–219. [PubMed]
  • Barry CD, Bosshard HE, Ellis RA, Marshall GR. Evolving macromodular molecular modeling system. Fed Proc. 1974 Dec;33(12):2368–2372. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...