4i3w
Structure of phosphonoacetaldehyde dehydrogenase in complex with gylceraldehyde-3-phosphate and cofactor NAD+
Structural highlights
FunctionPHNY_RHIME Plays an important role in phosphonate degradation by catalyzing the NAD-dependent conversion of phosphonoacetaldehyde (PnAA) to phosphonoacetate (PnA). Has low in vitro activity with the related compounds phosphonopropionaldehyde (3-oxopropyl phosphonate) and glyceraldehyde 3-phosphate.[1] Publication Abstract from PubMedPhosphonates (C-PO3(2-)) have applications as antibiotics, herbicides, and detergents. In some environments, these molecules represent the predominant source of phosphorus, and several microbes have evolved dedicated enzymatic machineries for phosphonate degradation. For example, most common naturally occurring phosphonates can be catabolized to either phosphonoacetaldehyde or phosphonoacetate, which can then be hydrolyzed to generate inorganic phosphate and acetaldehyde or acetate, respectively. The phosphonoacetaldehyde oxidase gene (phnY) links these two hydrolytic processes and provides a previously unknown catabolic mechanism for phosphonoacetate production in the microbial metabolome. Here, we present biochemical characterization of PhnY and high-resolution crystal structures of the apo state, as well as complexes with substrate, cofactor, and product. Kinetic analysis of active site mutants demonstrates how a highly conserved aldehyde dehydrogenase active site has been modified in nature to generate activity with a phosphonate substrate. Structure and function of phosphonoacetaldehyde dehydrogenase: the missing link in phosphonoacetate formation.,Agarwal V, Peck SC, Chen JH, Borisova SA, Chekan JR, van der Donk WA, Nair SK Chem Biol. 2014 Jan 16;21(1):125-35. doi: 10.1016/j.chembiol.2013.11.006. Epub, 2013 Dec 19. PMID:24361046[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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