42] Structure and posttranslational modification of lipoyl domain of 2-oxo-acid dehydrogenase multienzyme complexes

Abstract

Publisher Summary This chapter discusses the structure and posttranslational modification of lipoyl domain of 2-oxo-acid dehydrogenase multienzyme complexes. 2-oxo-acid dehydrogenase complexes catalyze the oxidative decarboxylation of a specific 2-oxo-acid and the subsequent acylation of coenzyme A, with the concomitant formation of NADH. A typical pyruvate dehydrogenase complex consists of multiple copies of three enzymes that act sequentially: pyruvate decarboxylase, dihydrolipoyl acetyltransferase, and dihydrolipoyl dehydrogenase. The E2 component is a multidomain polypeptide chain that aggregates with octahedral (24-mer) or icosahedral (60-mer) symmetry, depending on the source. The symmetry is dictated by the large C-terminal domain that also houses the acyltransferase active site. The N-terminal half of the polypeptide chain comprises one or more lipoyl domains and a peripheral subunit (E1/E3)-binding domain joined together by long and highly flexible linker regions of polypeptide chain. 2-oxo-acid dehydrogenase complexes specific for the oxidative decarboxylation of other 2-oxo acids—such as 2-oxoglutarate and branched-chain 2-oxo acids derived from the transamination of valine, leucine, and isoleucine—follow similar structural patterns. This chapter describes the purification of the lipoyl domain of the B. stearothermophilus pyruvate dehydrogenase complex and summarizes its solution structure. The chapter also describes the mechanism of posttranslational modification of the lipoyl domain, in particular, of the selection of the target lysine residue for lipoylation.