7m13 | pdb_00007m13
Crystal structure of CJ1428, a GDP-D-GLYCERO-L-GLUCO-HEPTOSE SYNTHASE from campylobacter jejuni in the presence of NADPH
Structural highlights
FunctionQ0P8I6_CAMJE Catalyzes the two-step NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction.[HAMAP-Rule:MF_00956] Publication Abstract from PubMedCampylobacter jejuni is the leading cause of food poisoning in the United States and Europe. The exterior cell surface of C. jejuni is coated with a capsular polysaccharide (CPS) that is essential for the maintenance and integrity of the bacterial cell wall and evasion of the host immune response. The identity and sequences of the monosaccharide components of the CPS are quite variable and dependent on the specific strain of C. jejuni. It is currently thought that the immediate precursor for the multiple variations found in the heptose moieties of the C. jejuni CPS is GDP-d-glycero-alpha-d-manno-heptose. In C. jejuni NCTC 11168, the heptose moiety is d-glycero-l-gluco-heptose. It has previously been shown that Cj1427 catalyzes the oxidation of GDP-d-glycero-alpha-d-manno-heptose to GDP-d-glycero-4-keto-alpha-d-lyxo-heptose using alpha-ketoglutarate as a cosubstrate. Cj1430 was now demonstrated to catalyze the double epimerization of this product at C3 and C5 to form GDP-d-glycero-4-keto-beta-l-xylo-heptose. Cj1428 subsequently catalyzes the stereospecific reduction of this GDP-linked heptose by NADPH to form GDP-d-glycero-beta-l-gluco-heptose. The three-dimensional crystal structure of Cj1430 was determined to a resolution of 1.85 A in the presence of bound GDP-d-glycero-beta-l-gluco-heptose, a product analogue. The structure shows that it belongs to the cupin superfamily. The three-dimensional crystal structure of Cj1428 was solved in the presence of NADPH to a resolution of 1.50 A. Its fold places it into the short-chain dehydrogenase/reductase superfamily. Typically, members in this family display a characteristic signature sequence of YXXXK, with the conserved tyrosine serving a key role in catalysis. In Cj1428, this residue is a phenylalanine. Biosynthesis of d-glycero-l-gluco-Heptose in the Capsular Polysaccharides of Campylobacter jejuni.,Huddleston JP, Anderson TK, Girardi NM, Thoden JB, Taylor Z, Holden HM, Raushel FM Biochemistry. 2021 Apr 26. doi: 10.1021/acs.biochem.1c00183. PMID:33900734[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
