Protein Family Models

This entry represents the catalytic domain of a group of lipoyl ligases/lipoyltransferases, such as Lipoate-protein ligase A/B (LipA/B) from E.coli and mammalian lipoyltransferases [1-5]. These proteins catalyse the transfer of the lipoyl group from lipoyl-AMP to the specific lysine residue of lipoyl domains of lipoate-dependent enzymes. Lipoic acid is an essential cofactor of the alpha-ketoacid dehydrogenase complexes and the glycine cleavage system. Paper describing PDB structure 1w66. [1]. 16735476. The Mycobacterium tuberculosis LipB enzyme functions as a cysteine/lysine dyad acyltransferase. Ma Q, Zhao X, Nasser Eddine A, Geerlof A, Li X, Cronan JE, Kaufmann SH, Wilmanns M;. Proc Natl Acad Sci U S A. 2006;103:8662-8667. Paper describing PDB structure 1x2g. [2]. 16043486. Crystal structure of lipoate-protein ligase A from Escherichia coli. Determination of the lipoic acid-binding site. Fujiwara K, Toma S, Okamura-Ikeda K, Motokawa Y, Nakagawa A, Taniguchi H;. J Biol Chem. 2005;280:33645-33651. Paper describing PDB structure 2ars. [3]. 16141198. Crystal structure of lipoate-protein ligase A bound with the activated intermediate: insights into interaction with lipoyl domains. Kim DJ, Kim KH, Lee HH, Lee SJ, Ha JY, Yoon HJ, Suh SW;. J Biol Chem. 2005;280:38081-38089. Paper describing PDB structure 2c7i. [4]. 16384580. Structure of a putative lipoate protein ligase from Thermoplasma acidophilum and the mechanism of target selection for post-translational modification. McManus E, Luisi BF, Perham RN;. J Mol Biol. 2006;356:625-637. Paper describing PDB structure 2e5a. [5]. 17570395. Crystal structure of bovine lipoyltransfer. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-21

This is the C-terminal domain of a bacterial lipoate protein ligase. There is no conservation between this C-terminus and that of vertebrate lipoate protein ligase C-termini, but both are associated with the domain BPL_LipA_LipB Pfam:PF03099, further upstream. This domain is required for adenylation of lipoic acid by lipoate protein ligases. The domain is not required for transfer of lipoic acid from the adenylate to the lipoyl domain. Upon adenylation, this domain rotates 180 degrees away from the active site cleft. Therefore, the domain does not interact with the lipoyl domain during transfer. [1]. 16384580. Structure of a putative lipoate protein ligase from Thermoplasma acidophilum and the mechanism of target selection for post-translational modification. McManus E, Luisi BF, Perham RN;. J Mol Biol. 2006;356:625-637. [2]. 19520844. The Thermoplasma acidophilum LplA-LplB complex defines a new class of bipartite lipoate-protein ligases. Christensen QH, Cronan JE;. J Biol Chem. 2009;284:21317-21326. [3]. 20089862. Global conformational change associated with the two-step reaction catalyzed by Escherichia coli lipoate-protein ligase A. Fujiwara K, Maita N, Hosaka H, Okamura-Ikeda K, Nakagawa A, Taniguchi H;. J Biol Chem. 2010;285:9971-9980. (from Pfam)

Date:

2024-10-16

This family includes biotin protein ligase, lipoate-protein ligase A and B. Biotin is covalently attached at the active site of certain enzymes that transfer carbon dioxide from bicarbonate to organic acids to form cellular metabolites. Biotin protein ligase (BPL) is the enzyme responsible for attaching biotin to a specific lysine at the active site of biotin enzymes. Each organism probably has only one BPL. Biotin attachment is a two step reaction that results in the formation of an amide linkage between the carboxyl group of biotin and the epsilon-amino group of the modified lysine [2]. Lipoate-protein ligase A (LPLA) catalyses the formation of an amide linkage between lipoic acid and a specific lysine residue in lipoate dependent enzymes [3]. The unusual biosynthesis pathway of lipoic acid is mechanistically intertwined with attachment of the cofactor [5]. [1]. 1409631. Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains. Wilson KP, Shewchuk LM, Brennan RG, Otsuka AJ, Matthews BW;. Proc Natl Acad Sci USA 1992;89:9257-9261. A comprehensive review of biotinylation. [2]. 10470036. The enzymatic biotinylation of proteins: a post-translational modification of exceptional specificity. Chapman-Smith A, Cronan JE Jr;. Trends Biochem Sci 1999;24:359-363. [3]. 8206909. Identification of the gene encoding lipoate-protein ligase A of Escherichia coli. Molecular cloning and characterization of the lplA gene and gene product. Morris TW, Reed KE, Cronan JE Jr;. J Biol Chem 1994;269:16091-16100. [4]. 11106165. Lipoylating and biotinylating enzymes contain a homo. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-16

lipoate--protein ligase A catalyzes both the ATP-dependent activation of exogenously supplied lipoate to lipoyl-AMP and the transfer of the activated lipoyl onto the lipoyl domains of lipoate-dependent enzymes; also catalyzes very poorly the transfer of lipoyl and octanoyl moiety from their acyl carrier protein

Date:

2019-06-18

Gene:

lplA

Date:

2021-02-10

Prokaryotic members of family TIGR00545 are lipoate--protein ligase, which first activates lipoic acid to lipoyl-AMP and then attaches it to the specific Lys side-chain of lipoate-dependent enzymes. Note that in mammalian systems, only the second half of the reaction is performed by this protein; biosynthesis of lipoyl-AMP is performed by a mitochondrial medium-chain acyl-CoA synthetase.

Date:

2024-06-11