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Publication Abstract from PubMed

The molybdenum storage protein (MoSto) deposits large amounts of molybdenum as polyoxomolybdate clusters in a heterohexameric (alphabeta)3 cage-like protein complex under ATP consumption. Here, we suggest a unique mechanism for the ATP-powered molybdate pumping process based on X-ray crystallography, cryoelectron microscopy, hydrogen-deuterium exchange mass spectrometry, and mutational studies of MoSto from Azotobacter vinelandii First, we show that molybdate, ATP, and Mg(2+) consecutively bind into the open ATP-binding groove of the beta-subunit, which thereafter becomes tightly locked by fixing the previously disordered N-terminal arm of the alpha-subunit over the beta-ATP. Next, we propose a nucleophilic attack of molybdate onto the gamma-phosphate of beta-ATP, analogous to the similar reaction of the structurally related UMP kinase. The formed instable phosphoric-molybdic anhydride becomes immediately hydrolyzed and, according to the current data, the released and accelerated molybdate is pressed through the cage wall, presumably by turning aside the Metbeta149 side chain. A structural comparison between MoSto and UMP kinase provides valuable insight into how an enzyme is converted into a molecular machine during evolution. The postulated direct conversion of chemical energy into kinetic energy via an activating molybdate kinase and an exothermic pyrophosphatase reaction to overcome a proteinous barrier represents a novelty in ATP-fueled biochemistry, because normally, ATP hydrolysis initiates large-scale conformational changes to drive a distant process.

Molybdate pumping into the molybdenum storage protein via an ATP-powered piercing mechanism.,Brunle S, Eisinger ML, Poppe J, Mills DJ, Langer JD, Vonck J, Ermler U Proc Natl Acad Sci U S A. 2019 Dec 6. pii: 1913031116. doi:, 10.1073/pnas.1913031116. PMID:31811022^[1]

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