PDBsum entry 1f12

Oxidoreductase

PDB id: 1f12

Contents

Protein chain

293 a.a. *

Ligands

3HC

Waters ×187

* Residue conservation analysis

PDB id:

1f12

Name:

Oxidoreductase

Title:

L-3-hydroxyacyl-coa dehydrogenase complexed with 3-hydroxybutyryl-coa

Structure:

L-3-hydroxyacyl-coa dehydrogenase. Chain: a, b. Synonym: schad. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: heart. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: protein was expressed with a c-terminal hexameric histidine tag.

Biol. unit:

Dimer (from PQS)

Resolution:

2.40Å R-factor: 0.212 R-free: 0.265

Authors:

J.J.Barycki,L.K.O'Brien,A.W.Strauss,L.J.Banaszak

Key ref:

J.J.Barycki et al. (2000). Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase. J Biol Chem, 275, 27186-27196. PubMed id: 10840044 DOI: 10.1074/jbc.M004669200

Date:

18-May-00 Release date: 27-Sep-00

Protein chains

Q16836  (HCDH_HUMAN) -  Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial from Homo sapiens

Seq: 314 a.a.

Struc: 293 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.1.1.1.35 - 3-hydroxyacyl-CoA dehydrogenase.
• Reaction: a (3S)-3-hydroxyacyl-CoA + NAD⁺ = a 3-oxoacyl-CoA + NADH + H⁺

(3S)-3-hydroxyacyl-CoA (Bound ligand (Het Group name = 3HC) matches with 96.36% similarity) + NAD(+) = 3-oxoacyl-CoA + NADH + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M004669200

J Biol Chem 275:27186-27196 (2000)

PubMed id: 10840044

Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase.

J.J.Barycki, L.K.O'Brien, A.W.Strauss, L.J.Banaszak.

ABSTRACT

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.

Selected figure(s)

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.

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.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 27186-27196) copyright 2000.

Figures were selected by an automated process.