Open AccessAn Investigation of the Active Site of Lactate Dehydrogenase with NAD + Analogues
Author(s) -
SAMAMA JeanPierre,
MARCHALROSENHEIMER Nicole,
BEIELLMANN JeanFrancois,
ROSSMANN Michael G.
Publication year - 1981
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1981.tb05737.x
Subject(s) - nad+ kinase , cofactor , chemistry , moiety , nicotinamide adenine dinucleotide , stereochemistry , lactate dehydrogenase , nicotinamide , dehydrogenase , enzyme , amide , pyridinium , biochemistry , medicinal chemistry
The kinetic properties of 18 NAD + analogues, with alterations to the nicotinamide moiety, have been studied with respect to dogfish M 4 , rabbit M 4 and beef H 4 lactate dehydrogenases. The size of the groups present at C‐3 of the pyridinium can be increased quite extensively without loss of coenzyme activity. Groups tested were thioamide, methyl, ethyl, diazoketone and chloroacetyl. Substitutions at positions C‐4 and C‐5 prevent proper positioning for hydride transfer and can hinder binding to the enzyme. The kinetic properties of pyridine‐adenine dinucleotide and its 3‐iodo derivative reveal the bidning role of the amide at C‐3 whereas 3‐cyanopyridine‐adenine dinculeotide is a strong inhibitor.