IUBMB Enzyme Nomenclature

EC 2.7.7.63

Accepted name: lipoate—protein ligase

Reaction: (1) ATP + lipoate = diphosphate + lipoyl-AMP
(2) lipoyl-AMP + apoprotein = protein N6-(lipoyl)lysine + AMP

Other name(s): LplA; lipoate protein ligase; lipoate-protein ligase A; LPL; LPL-B

Systematic name: ATP:lipoate adenylyltransferase

Comments: Requires Mg2+. Selenolipoate and 6-thio-octanoate can also act as substrates, but more slowly [2]. Both D- and L-lipoate can act as a substrate but there is a preference for the naturally occurring D-form. The lipoyl cofactor is essential for the function of several key enzymes involved in oxidative metabolism, including pyruvate dehydrogenase (E2 domain), 2-oxoglutarate dehydrogenase (E2 domain), the branched-chain 2-oxoacid dehydrogenases and the glycine cleavage system (H protein) [6]. This enzyme attaches lipoic acid to the lipoyl domains of these proteins. The remaining steps in the production of lipoyl cofactor involve EC 2.3.1.181, lipoyl(octanoyl) transferase and EC 2.8.1.8, lipoyl synthase.

Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 144114-18-1

References:

1. Morris, T.W., Reed, K.E. and Cronan, J.E., Jr. Identification of the gene encoding lipoate-protein ligase A of Escherichia coli. Molecular cloning and characterization of the lplA gene and gene product. J. Biol. Chem. 269 (1994) 16091-16100. [PMID: 8206909]

2. Green, D.E., Morris, T.W., Green, J., Cronan, J.E., Jr. and Guest, J.R. Purification and properties of the lipoate protein ligase of Escherichia coli. Biochem. J. 309 (1995) 853-862. [PMID: 7639702]

3. Zhao, X., Miller, J.R., Jiang, Y., Marletta, M.A. and Cronan, J.E. Assembly of the covalent linkage between lipoic acid and its cognate enzymes. Chem. Biol. 10 (2003) 1293-1302. [PMID: 14700636]

4. Kim do, J., Kim, K.H., Lee, H.H., Lee, S.J., Ha, J.Y., Yoon, H.J. and Suh, S.W. Crystal structure of lipoate-protein ligase A bound with the activated intermediate: insights into interaction with lipoyl domains. J. Biol. Chem. 280 (2005) 38081-38089. [PMID: 16141198]

5. Fujiwara, K., Toma, S., Okamura-Ikeda, K., Motokawa, Y., Nakagawa, A. and Taniguchi, H. Crystal structure of lipoate-protein ligase A from Escherichia coli. Determination of the lipoic acid-binding site. J. Biol. Chem. 280 (2005) 33645-33651. [PMID: 16043486]

6. Jordan, S.W. and Cronan, J.E., Jr. A new metabolic link. The acyl carrier protein of lipid synthesis donates lipoic acid to the pyruvate dehydrogenase complex in Escherichia coli and mitochondria. J. Biol. Chem. 272 (1997) 17903-17906. [PMID: 9218413]

[EC 2.7.7.63 created 2006]


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