Birktoft J J, Fernley R T, Bradshaw R A, Banaszak L J
Proc Natl Acad Sci U S A. 1982 Oct;79(20):6166-70. doi: 10.1073/pnas.79.20.6166.
The amino acid sequence of porcine heart mitochondrial malate dehydrogenase (mMDH; L-malate: NAD+ oxidoreductase, EC 1.1.1.37) has been compared with the sequences of six different lactate dehydrogenases (LDH; L-lactate: NAD+ oxidoreductase, EC 1.1.1.27) and with the "x-ray" sequence of cytoplasmic malate dehydrogenase (sMDH). The main points are that (i) all three enzymes are homologous; (ii) invariant residues in the catalytic center of these enzymes include a histidine and an internally located aspartate that function as a proton relay system; (iii) numerous residues important to coenzyme binding are conserved, including several glycines and charged residues; and (iv) amino acid side chains present in the subunit interface common to the MDHs and LDHs appear to be better conserved than those in the protein interior. It is concluded that LDH, sMDH, and mMDH are derived from a common ancestral gene and probably have similar catalytic mechanisms.
已将猪心脏线粒体苹果酸脱氢酶（mMDH；L-苹果酸：NAD⁺氧化还原酶，EC 1.1.1.37）的氨基酸序列与六种不同乳酸脱氢酶（LDH；L-乳酸：NAD⁺氧化还原酶，EC 1.1.1.27）的序列以及细胞质苹果酸脱氢酶（sMDH）的“X射线”序列进行了比较。主要要点如下：（i）这三种酶具有同源性；（ii）这些酶催化中心的不变残基包括一个组氨酸和一个位于内部的天冬氨酸，它们作为质子传递系统发挥作用；（iii）许多对辅酶结合很重要的残基是保守的，包括几个甘氨酸和带电荷的残基；（iv）MDH和LDH亚基界面中存在的氨基酸侧链似乎比蛋白质内部的侧链保守性更好。得出的结论是，LDH、sMDH和mMDH源自一个共同的祖先基因，并且可能具有相似的催化机制。
