InterPro domain: IPR015955

This entry represents a structural motif found at the C-terminal of lactate dehydrogenase ( 1.1.1.27 )and malate dehydrogenases ( 1.1.1.37 ), as well as at the C-terminal of family 4 glycoside hydrolases ( 3.2.1 ). These domains have an unusual fold consisting of segregated alpha-helical and beta-sheet regions, although they contain predominantly anti-parallel beta-sheets [ 1 , 2 , 3 ].

L-lactate dehydrogenases are metabolic enzymes that catalyse the conversion of L-lactate to pyruvate, the last step in anaerobic glycolysis. L-lactate dehydrogenase is also found as a lens crystallin in bird and crocodile eyes. Malate dehydrogenases catalyse the interconversion of malate to oxaloacetate. The enzyme participates in the citric acid cycle.

O-Glycosyl hydrolases 3.2.1. are a widespread group of enzymes that hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families [ 4 , 5 ]. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. Because the fold of proteins is better conserved than their sequences, some of the families can be grouped in 'clans'. Glycoside hydrolase family 4 GH4 comprises enzymes with several known activities; 6-phospho-beta-glucosidase ( 3.2.1.86 ); 6-phospho-alpha-glucosidase ( 3.2.1.122 ); alpha-galactosidase ( 3.2.1.22 ).

1. Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase. Proteins 43, 175-85
2. Refined crystal structure of mitochondrial malate dehydrogenase from porcine heart and the consensus structure for dicarboxylic acid oxidoreductases. Biochemistry 33, 2078-88
3. Crystal structure of Thermotoga maritima alpha-glucosidase AglA defines a new clan of NAD+-dependent glycosidases. J. Biol. Chem. 278, 19151-8
4. Conserved catalytic machinery and the prediction of a common fold for several families of glycosyl hydrolases. Proc. Natl. Acad. Sci. U.S.A. 92, 7090-4
5. Structures and mechanisms of glycosyl hydrolases. Structure 3, 853-9