PDBsum entry 1i10

Oxidoreductase

PDB id: 1i10

Contents

Protein chain

(+ 2 more) 331 a.a. *

Ligands

ACT ×8

NAI ×8

OXM ×8

Waters ×652

* Residue conservation analysis

PDB id:

1i10

Name:

Oxidoreductase

Title:

Human muscle l-lactate dehydrogenase m chain, ternary complex with nadh and oxamate

Structure:

L-lactate dehydrogenase m chain. Chain: a, b, c, d, e, f, g, h. Synonym: ldh-a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: heart. Gene: ldha. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Tetramer (from PQS)

Resolution:

2.30Å R-factor: 0.200 R-free: 0.257

Authors:

J.A.Read,V.J.Winter,C.M.Eszes,R.B.Sessions,R.L.Brady

Key ref:

J.A.Read et al. (2001). Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase. Proteins, 43, 175-185. PubMed id: 11276087

Date:

30-Jan-01 Release date: 28-Mar-01

Protein chains

P00338  (LDHA_HUMAN) -  L-lactate dehydrogenase A chain from Homo sapiens

Seq: 332 a.a.

Struc: 331 a.a.

Enzyme reactions

• Enzyme class: E.C.1.1.1.27 - L-lactate dehydrogenase.
• Reaction: (S)-lactate + NAD⁺ = pyruvate + NADH + H⁺

(S)-lactate (Bound ligand (Het Group name = OXM) matches with 71.43% similarity) + NAD(+) (Bound ligand (Het Group name = NAI) corresponds exactly) = pyruvate + NADH + H(+)

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

reference

Proteins 43:175-185 (2001)

PubMed id: 11276087

Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase.

J.A.Read, V.J.Winter, C.M.Eszes, R.B.Sessions, R.L.Brady.

ABSTRACT

Lactate dehydrogenase (LDH) interconverts pyruvate and lactate with concomitant interconversion of NADH and NAD(+). Although crystal structures of a variety of LDH have previously been described, a notable absence has been any of the three known human forms of this glycolytic enzyme. We have now determined the crystal structures of two isoforms of human LDH-the M form, predominantly found in muscle; and the H form, found mainly in cardiac muscle. Both structures have been crystallized as ternary complexes in the presence of the NADH cofactor and oxamate, a substrate-like inhibitor. Although each of these isoforms has different kinetic properties, the domain structure, subunit association, and active-site regions are indistinguishable between the two structures. The pK(a) that governs the K(M) for pyruvate for the two isozymes is found to differ by about 0.94 pH units, consistent with variation in pK(a) of the active-site histidine. The close similarity of these crystal structures suggests the distinctive activity of these enzyme isoforms is likely to result directly from variation of charged surface residues peripheral to the active site, a hypothesis supported by electrostatic calculations based on each structure. Proteins 2001;43:175-185.