Structure of dihydrodipicolinate synthase from the commensal bacteriumBacteroides thetaiotaomicronat 2.1 Å resolution

Abstract

Dihydrodipicolinate synthase (DapA) catalyzes the first committed step of the diaminopimelate biosynthetic pathway of lysine. It has been shown to be an essential enzyme in many bacteria and has been the subject of research to generate novel antibiotics. However, this pathway is present in both pathogenic and commensal bacteria, and antibiotics targeting DapA may interfere with normal gut colonization. Bacteroides thetaiotaomicron is a Gram-negative commensal bacterium that makes up a large proportion of the normal microbiota of the human gut. The structure of DapA from B. thetaiotaomicron (BtDapA) has been determined. This structure will help to guide the generation of selectively active antibiotic compounds targeting DapA.

Cloning, expression, purification, crystallization and X-ray diffraction analysis of dihydrodipicolinate synthase from the human pathogenic bacteriumBartonella henselaestrain Houston-1 at 2.1 Å resolution

“…2). Based on the fact that the gene is essential in bacteria and is a putative target for antibiotic development, there have been numerous studies regarding the structure of DapA from a number of pathogenic bacteria such as Escherichia coli, Mycobacterium tuberculosis, Neisseria meningitidis, Pseudomonas aeruginosa, Staphylococcus aureus and Bacteriodes thetaiotaomicron, which is an endosymbiont of the human gut (Dobson et al, 2005;Kefala et al, 2008;Devenish et al, 2009;Kaur et al, 2011;Burgess et al, 2008;Girish et al, 2008;Mank et al, 2015). Although there has been a move to change the name of the enzyme to 4-hydroxytetrahydrodipicolinate synthase, we will use the more common enzyme name here (Bochaute et al, 2013).…”