3d31

Publication Abstract from PubMed

Transport across cellular membranes is an essential process that is catalyzed by diverse membrane transport proteins. The turnover rates of certain transporters are inhibited by their substrates in a process termed trans-inhibition, whose structural basis is poorly understood. Here we present the crystal structure of a molybdate/tungstate ABC transporter (ModBC) from Methanosarcina acetivorans in a trans-inhibited state. The regulatory domains of the nucleotide-binding subunits are in close contact and provide two oxyanion binding pockets at the shared interface. By specifically binding to these pockets, molybdate or tungstate prevent ATPase activity and lock the transporter in an inward-facing conformation, with the catalytic motifs of the nucleotide-binding domains separated. This allosteric effect prevents the transporter from switching between the inward-facing and the outward-facing states, thus interfering with the alternating access and release mechanism.

Structural Basis of Trans-Inhibition in a Molybdate/tungstate ABC Transporter.,Gerber S, Comellas-Bigler M, Goetz BA, Locher KP Science. 2008 May 29;. PMID:18511655^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.