1I10

HUMAN MUSCLE L-LACTATE DEHYDROGENASE M CHAIN, TERNARY COMPLEX WITH NADH AND OXAMATE

1I10 の概要

• エントリーDOI: 10.2210/pdb1i10/pdb
• 関連するPDBエントリー: 1I0Z 1ldg 5ldh 9ldt
• 分子名称: L-LACTATE DEHYDROGENASE M CHAIN, ACETATE ION, 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE, ... (5 entities in total)
• 機能のキーワード: dehydrogenase, rossmann fold, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P00338
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 299336.06

構造登録者

Read, J.A.,Winter, V.J.,Eszes, C.M.,Sessions, R.B.,Brady, R.L. (登録日: 2001-01-30, 公開日: 2001-03-28, 最終更新日: 2023-08-09)

主引用文献

Read, J.A.,Winter, V.J.,Eszes, C.M.,Sessions, R.B.,Brady, R.L.
Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase.
Proteins, 43:175-185, 2001

PubMed 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.

PubMed: 11276087
DOI: 10.1002/1097-0134(20010501)43:2<175::AID-PROT1029>3.0.CO;2-#

実験手法

X-RAY DIFFRACTION (2.3 Å)