5TV6

A. aeolicus BioW with pimelate

Summary for 5TV6

• Entry DOI: 10.2210/pdb5tv6/pdb
• Related: 5TV5 5TV8 5TVA
• Descriptor: 6-carboxyhexanoate--CoA ligase, PIMELIC ACID (3 entities in total)
• Functional Keywords: pimeloyl-coa ligase, adenylation, ligase
• Biological source: Aquifex aeolicus
• Total number of polymer chains: 2
• Total formula weight: 55681.05

Authors

Estrada, P.,Manandhar, M.,Dong, S.-H.,Deveryshetty, J.,Agarwal, V.,Cronan, J.E.,Nair, S.K. (deposition date: 2016-11-08, release date: 2016-12-07, Last modification date: 2024-10-30)

Primary citation

Estrada, P.,Manandhar, M.,Dong, S.H.,Deveryshetty, J.,Agarwal, V.,Cronan, J.E.,Nair, S.K.
The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming enzymes.
Nat. Chem. Biol., 13:668-674, 2017

PubMed Abstract: Reactions that activate carboxylates through acyl-adenylate intermediates are found throughout biology and include acyl- and aryl-CoA synthetases and tRNA synthetases. Here we describe the characterization of Aquifex aeolicus BioW, which represents a new protein fold within the superfamily of adenylating enzymes. Substrate-bound structures identified the enzyme active site and elucidated the mechanistic strategy for conjugating CoA to the seven-carbon α,ω-dicarboxylate pimelate, a biotin precursor. Proper position of reactive groups for the two half-reactions is achieved solely through movements of active site residues, as confirmed by site-directed mutational analysis. The ability of BioW to hydrolyze adenylates of noncognate substrates is reminiscent of pre-transfer proofreading observed in some tRNA synthetases, and we show that this activity can be abolished by mutation of a single residue. These studies illustrate how BioW can carry out three different biologically prevalent chemical reactions (adenylation, thioesterification, and proofreading) in the context of a new protein fold.

PubMed: 28414711
DOI: 10.1038/nchembio.2359

Experimental method

X-RAY DIFFRACTION (2.456 Å)