This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mycobacterium tuberculosis utilizes a sulfur transfer protein mechanism to biosynthesize cysteine when exposed to the oxidative stress environment upon phagocytosis by a macrophage. This system involves the proteins Rv1335 (CysO) and Rv1336 (CysM). An alternative pathway to cysteine in M. tuberculosis exists, but uses sulfide as the sulfur source, which is readily oxidized to sulfate when exposed to oxidizing agents. M. tuberculosis has evolved the ability to utilize a ubiquitin like protein as a sulfur transfer protein, CysO, to serve as the sulfur source by generating a less reactive thio-caryboxy C-terminus. CysO is able to deliver the sulfur atom through its flexible digylcyl C-terminus into the active site of CysM, which is a pyridoxyl 5'-phosphate utilizing b-elimination enzyme. In Archaea, orthologous genes responsible for the first two steps of the aromatic amino acid biosynthesis leading to 3-dehydroquinate (DHQ) are missing. Recently, two protein products from Methanocaldococcus jannaschii, Mj0400 and Mj1249, have been reported as the nonorthologous catalysts of the DHQ formation. Crystal structures of these enzymes assisted the identification of the substrates and the elucidation of their catalytic mechanisms. Structures have been solved and papers published.
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