2WYU

High resolution structure of Thermus thermophilus enoyl-acyl carrier protein reductase apo-form

Summary for 2WYU

• Entry DOI: 10.2210/pdb2wyu/pdb
• Related: 1ULU 2WYV 2WYW
• Descriptor: ENOYL-[ACYL CARRIER PROTEIN] REDUCTASE, GLYCEROL, SODIUM ION, ... (4 entities in total)
• Functional Keywords: oxidoreductase, fatty acid biosynthesis, oxidation reduction
• Biological source: THERMUS THERMOPHILUS
• Total number of polymer chains: 4
• Total formula weight: 112818.89

Authors

Otero, J.M.,Noel, A.J.,Guardado-Calvo, P.,Llamas-Saiz, A.L.,van Raaij, M.J. (deposition date: 2009-11-20, release date: 2010-11-24, Last modification date: 2023-12-20)

Primary citation

Otero, J.M.,Noel, A.J.,Guardado-Calvo, P.,Llamas-Saiz, A.L.,Wende, W.,Schierling, B.,Pingoud, A.,van Raaij, M.J.
High-resolution structures of Thermus thermophilus enoyl-acyl carrier protein reductase in the apo form, in complex with NAD+ and in complex with NAD+ and triclosan.
Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun., 68:1139-1148, 2012

PubMed Abstract: Enoyl-acyl carrier protein reductase (ENR; the product of the fabI gene) is an important enzyme that is involved in the type II fatty-acid-synthesis pathway of bacteria, plants, apicomplexan protozoa and mitochondria. Harmful pathogens such as Mycobacterium tuberculosis and Plasmodium falciparum use the type II fatty-acid-synthesis system, but not mammals or fungi, which contain a type I fatty-acid-synthesis pathway consisting of one or two multifunctional enzymes. For this reason, specific inhibitors of ENR are attractive antibiotic candidates. Triclosan, a broad-range antibacterial agent, binds to ENR, inhibiting fatty-acid synthesis. As humans do not have an ENR enzyme, they are not affected. Here, high-resolution structures of Thermus thermophilus (Tth) ENR in the apo form, bound to NAD(+) and bound to NAD(+) plus triclosan are reported. Differences from and similarities to other known ENR structures are reported; in general, the structures are very similar. The cofactor-binding site is also very similar to those of other ENRs and, as reported for other species, triclosan leads to greater ordering of the loop that covers the cofactor-binding site, which, together with the presence of triclosan itself, presumably provides tight binding of the dinucleotide, preventing cycling of the cofactor. Differences between the structures of Tth ENR and other ENRs are the presence of an additional β-sheet at the N-terminus and a larger number of salt bridges and side-chain hydrogen bonds. These features may be related to the high thermal stability of Tth ENR.

PubMed: 23027736
DOI: 10.1107/S1744309112033982

Experimental method

X-RAY DIFFRACTION (1.5 Å)