2art

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spinqualitylabelsall models 2art, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of lipoate-protein ligase A bound with lipoyl-AMP

Overview

Lipoic acid is the covalently attached cofactor of several multi-component, enzyme complexes that catalyze key metabolic reactions. Attachment of, lipoic acid to the lipoyl-dependent enzymes is catalyzed by, lipoate-protein ligases (LPLs). In Escherichia coli, two distinct enzymes, lipoate-protein ligase A (LplA) and lipB-encoded lipoyltransferase (LipB), catalyze independent pathways for lipoylation of the target proteins. The, reaction catalyzed by LplA occurs in two steps. First, LplA activates, exogenously supplied lipoic acid at the expense of ATP to lipoyl-AMP., Next, it transfers the enzyme-bound lipoyl-AMP to the epsilon-amino group, of a specific lysine residue of the lipoyl domain to give an amide, linkage. To gain insight into the mechanism of action by LplA, we have, determined the crystal structure of Thermoplasma acidophilum LplA in three, forms: (i) the apo form; (ii) the ATP complex; and (iii) the lipoyl-AMP, complex. The overall fold of LplA bears some resemblance to that of the, biotinyl protein ligase module of the E. coli biotin holoenzyme, synthetase/bio repressor (BirA). Lipoyl-AMP is bound deeply in the, bifurcated pocket of LplA and adopts a U-shaped conformation. Only the, phosphate group and part of the ribose sugar of lipoyl-AMP are accessible, from the bulk solvent through a tunnel-like passage, whereas the rest of, the activated intermediate is completely buried inside the active site, pocket. This first view of the activated intermediate bound to LplA, allowed us to propose a model of the complexes between Ta LplA and lipoyl, domains, thus shedding light on the target protein/lysine residue, specificity of LplA.

About this Structure

2ART is a Single protein structure of sequence from Thermoplasma acidophilum with MG, LPA and AMP as ligands. Full crystallographic information is available from OCA.

Reference

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 Nov 11;280(45):38081-9. Epub 2005 Sep 2. PMID:16141198

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