7ag4
From Proteopedia
Crystal structure of active site mutant of SQ Isomerase (YihS-H248A) from Salmonella enterica in complex with sulfofructose (SF)
Structural highlights
FunctionSQUS_SALTY Catalyzes the isomerization of sulfoquinovose (SQ) to 6-deoxy-6-sulfo-D-fructose (SF) (By similarity). In vitro, can also catalyze the interconversion of mannose, fructose and glucose, but has extremely low activity with glucose.[HAMAP-Rule:MF_00998][1] Publication Abstract from PubMedThe sulfosugar sulfoquinovose (SQ) is produced by essentially all photosynthetic organisms on Earth and is metabolized by bacteria through the process of sulfoglycolysis. The sulfoglycolytic Embden-Meyerhof-Parnas pathway metabolizes SQ to produce dihydroxyacetone phosphate and sulfolactaldehyde and is analogous to the classical Embden-Meyerhof-Parnas glycolysis pathway for the metabolism of glucose-6-phosphate, though the former only provides one C3 fragment to central metabolism, with excretion of the other C3 fragment as dihydroxypropanesulfonate. Here, we report a comprehensive structural and biochemical analysis of the three core steps of sulfoglycolysis catalyzed by SQ isomerase, sulfofructose (SF) kinase, and sulfofructose-1-phosphate (SFP) aldolase. Our data show that despite the superficial similarity of this pathway to glycolysis, the sulfoglycolytic enzymes are specific for SQ metabolites and are not catalytically active on related metabolites from glycolytic pathways. This observation is rationalized by three-dimensional structures of each enzyme, which reveal the presence of conserved sulfonate binding pockets. We show that SQ isomerase acts preferentially on the beta-anomer of SQ and reversibly produces both SF and sulforhamnose (SR), a previously unknown sugar that acts as a derepressor for the transcriptional repressor CsqR that regulates SQ-utilization. We also demonstrate that SF kinase is a key regulatory enzyme for the pathway that experiences complex modulation by the metabolites SQ, SLA, AMP, ADP, ATP, F6P, FBP, PEP, DHAP, and citrate, and we show that SFP aldolase reversibly synthesizes SFP. This body of work provides fresh insights into the mechanism, specificity, and regulation of sulfoglycolysis and has important implications for understanding how this biochemistry interfaces with central metabolism in prokaryotes to process this major repository of biogeochemical sulfur. Molecular Basis of Sulfosugar Selectivity in Sulfoglycolysis.,Sharma M, Abayakoon P, Epa R, Jin Y, Lingford JP, Shimada T, Nakano M, Mui JW, Ishihama A, Goddard-Borger ED, Davies GJ, Williams SJ ACS Cent Sci. 2021 Mar 24;7(3):476-487. doi: 10.1021/acscentsci.0c01285. Epub, 2021 Feb 23. PMID:33791429[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
