PDBsum entry 1cme

Oxidoreductase(NAD(a)-choh(d))

PDB id: 1cme

Contents

Protein chain

312 a.a.

Ligands

MLT

NAD

Waters ×88

Theoretical model

PDB id:

1cme

Name:

Oxidoreductase(NAD(a)-choh(d))

Structure:

Malate dehydrogenase complex with malate and NAD (theoretical model)

Source:

(Escherichia coli)

Authors:

M.D.Hall,L.J.Banaszak

Key ref:

M.D.Hall et al. (1992). Crystal structure of Escherichia coli malate dehydrogenase. A complex of the apoenzyme and citrate at 1.87 A resolution. J Mol Biol, 226, 867-882. PubMed id: 1507230 DOI: 10.1016/0022-2836(92)90637-Y

Date:

21-Mar-92 Release date: 31-Jan-94

Protein chain

No UniProt id for this chain

Struc: 312 a.a.

Enzyme reactions

• Enzyme class: E.C.1.1.1.37 - malate dehydrogenase.
• Pathway: Citric acid cycle
• Reaction: (S)-malate + NAD⁺ = oxaloacetate + NADH + H⁺

(S)-malate (Bound ligand (Het Group name = MLT) matches with 1000.00% similarity corresponds exactly) + NAD(+) = oxaloacetate + NADH + H(+)

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

reference

DOI no: 10.1016/0022-2836(92)90637-Y

J Mol Biol 226:867-882 (1992)

PubMed id: 1507230

Crystal structure of Escherichia coli malate dehydrogenase. A complex of the apoenzyme and citrate at 1.87 A resolution.

M.D.Hall, D.G.Levitt, L.J.Banaszak.

ABSTRACT

The crystal structure of malate dehydrogenase from Escherichia coli has been determined with a resulting R-factor of 0.187 for X-ray data from 8.0 to 1.87 A. Molecular replacement, using the partially refined structure of porcine mitochondrial malate dehydrogenase as a probe, provided initial phases. The structure of this prokaryotic enzyme is closely homologous with the mitochondrial enzyme but somewhat less similar to cytosolic malate dehydrogenase from eukaryotes. However, all three enzymes are dimeric and form the subunit-subunit interface through similar surface regions. A citrate ion, found in the active site, helps define the residues involved in substrate binding and catalysis. Two arginine residues, R81 and R153, interacting with the citrate are believed to confer substrate specificity. The hydroxyl of the citrate is hydrogen-bonded to a histidine, H177, and similar interactions could be assigned to a bound malate or oxaloacetate. Histidine 177 is also hydrogen-bonded to an aspartate, D150, to form a classic His.Asp pair. Studies of the active site cavity indicate that the bound citrate would occupy part of the site needed for the coenzyme. In a model building study, the cofactor, NAD, was placed into the coenzyme site which exists when the citrate was converted to malate and crystallographic water molecules removed. This hypothetical model of a ternary complex was energy minimized for comparison with the structure of the binary complex of porcine cytosolic malate dehydrogenase. Many residues involved in cofactor binding in the minimized E. coli malate dehydrogenase structure are homologous to coenzyme binding residues in cytosolic malate dehydrogenase. In the energy minimized structure of the ternary complex, the C-4 atom of NAD is in van der Waals' contact with the C-3 atom of the malate. A catalytic cycle involves hydride transfer between these two atoms.

Selected figure(s)

Figure 7.
Figure 7. Sp filfing model of' the NAI) vavit)~. (a) 7'hv tjop t~errodiagram represents n o~~arall \-iew of tlw KA41) (*:ivity with citrate in thi active site in a bac~kbone model of' the protein. All filled-in aeas belong to the (:a~i&y. (1)) The middle diagram represents a dose-up view of the X'AD binding wvity wit,h citrate in the active sit)e. All side-c:hnins ~II wntwt with the cavit,y are shown. (c) The bot,tom iagram represents the same feabres shown in (1)): ho\rrver. t'hr c*itrste has been c~hanged to rrpresent a malatr molrculc.

Figure 8.
Figure 8. Hypothetical model of P;AD in the active site of rMDHase. The stereodrawing shows the conformation of the XAD with malatr as found in the energy minimized structure of the eMDHase--NSD-malate complex. X&hods used to obtain this structure are described more fully in the text. Atoms involved in hydrogen bonding t,o the protein are labeled. Hydrogen bonds found between the malate and active site residues are shown by broken lines. 4 single heavy broken line drpic+s the trajectory of hydride ion transfer during catalysis.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1992, 226, 867-882) copyright 1992.

Figures were selected by an automated process.