3E7X

Crystal structure of DLTA: implications for the reaction mechanism of non-ribosomal peptide synthetase (NRPS) adenylation domains

Summary for 3E7X

• Entry DOI: 10.2210/pdb3e7x/pdb
• Related: 1AMU 1BA3 1HQB 1MD9 1PG4 2DLS 3E7W
• Descriptor: D-alanine--poly(phosphoribitol) ligase subunit 1, ADENOSINE MONOPHOSPHATE (3 entities in total)
• Functional Keywords: dlta, non-ribosomal peptide synthetase, nrps, adenylation domain, d-alanylation, d-alanine-dalanyl, amp, cytoplasm, ligase
• Biological source: Bacillus subtilis
• Cellular location: Cytoplasm (Probable): P39581
• Total number of polymer chains: 1
• Total formula weight: 57284.62

Authors

Yonus, H.,Neumann, P.,Zimmermann, S.,May, J.J.,Marahiel, M.A.,Stubbs, M.T. (deposition date: 2008-08-19, release date: 2008-09-09, Last modification date: 2023-11-01)

Primary citation

Yonus, H.,Neumann, P.,Zimmermann, S.,May, J.J.,Marahiel, M.A.,Stubbs, M.T.
Crystal structure of DltA. Implications for the reaction mechanism of non-ribosomal peptide synthetase adenylation domains
J.Biol.Chem., 283:32484-32491, 2008

PubMed Abstract: DltA, the D-alanine:D-alanyl carrier protein ligase responsible for the initial step of lipoteichoic acid D-alanylation in Gram-positive bacteria, belongs to the adenylation domain superfamily, which also includes acetyl-CoA synthetase and the adenylation domains of non-ribosomal synthetases. The two-step reaction catalyzed by these enzymes (substrate adenylation followed by transfer to the reactive thiol group of CoA or the phosphopantheinyl prosthetic group of peptidyl carrier proteins) has been suggested to proceed via large scale rearrangements of structural domains within the enzyme. The structures of DltA reported here reveal the determinants for D-Ala substrate specificity and confirm that the peptidyl carrier protein-activating domains are able to adopt multiple conformational states, in this case corresponding to the thiolation reaction. Comparisons of available structures allow us to propose a mechanism whereby small perturbations of finely balanced metastable structural states would be able to direct an ordered formation of non-ribosomal synthetase products.

PubMed: 18784082
DOI: 10.1074/jbc.M800557200

Experimental method

X-RAY DIFFRACTION (2.6 Å)