2hxt

Crystal structure of L-Fuconate Dehydratase from Xanthomonas campestris liganded with Mg++ and D-erythronohydroxamate

spinqualitylabelsall models 2hxt, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2hxt is a 1 chain structure with sequence from Xanthomonas campestris pv. campestris. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Ligands: EHM, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FUCD_XANCP Plays a role in the catabolism of L-fucose. Catalyzes the dehydration of L-fuconate to 2-keto-3-deoxy-L-fuconate by the abstraction of the 2-proton to generate an enediolate intermediate that is stabilized by the magnesium ion. L-fuconate is the preferred substrate with 15-fold lower activity observed for L-galactonate and 8-fold lower activity with D-arabinonate. No activity detected with D-fuconate. Can also catalyze the epimerization of L-talonate and D-ribonate, but at slow rates. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Many members of the mechanistically diverse enolase superfamily have unknown functions. In this report we use both genome (operon) context and screening of a library of acid sugars to assign the L-fuconate dehydratase (FucD) function to a member of the mandelate racemase (MR) subgroup of the superfamily encoded by the Xanthomonas campestris pv. campestris str. ATCC 33913 genome (GI:21233491). Orthologues of FucD are found in both bacteria and eukaryotes, the latter including the rTS beta protein in Homo sapiens that has been implicated in regulating thymidylate synthase activity. As suggested by sequence alignments and confirmed by high-resolution structures in the presence of active site ligands, FucD and MR share the same active site motif of functional groups: three carboxylate ligands for the essential Mg2+ located at the ends of the third, fourth, and fifth beta-strands in the (beta/alpha)7beta-barrel domain (Asp 248, Glu 274, and Glu 301, respectively), a Lys-x-Lys motif at the end of the second beta-strand (Lys 218 and Lys 220), a His-Asp dyad at the end of the seventh and beta-strands (His 351 and Asp 324, respectively), and a Glu at the end of the eighth beta-strand (Glu 382). The mechanism of the FucD reaction involves initial abstraction of the 2-proton by Lys 220, acid catalysis of the vinylogous beta-elimination of the 3-OH group by His 351, and stereospecific ketonization of the resulting enol, likely by the conjugate acid of Lys 220, to yield the 2-keto-3-deoxy-L-fuconate product. Screening of the library of acid sugars revealed substrate and functional promiscuity: In addition to L-fuconate, FucD also catalyzes the dehydration of L-galactonate, D-arabinonate, D-altronate, L-talonate, and D-ribonate. The dehydrations of L-fuconate, L-galactonate, and D-arabinonate are initiated by abstraction of the 2-protons by Lys 220. The dehydrations of L-talonate and D-ribonate are initiated by abstraction of the 2-protons by His 351; however, protonation of the enediolate intermediates by the conjugate acid of Lys 220 yields L-galactonate and D-arabinonate in competition with dehydration. The functional promiscuity discovered for FucD highlights possible structural mechanisms for evolution of function in the enolase superfamily. Evolution of enzymatic activities in the enolase superfamily: L-fuconate dehydratase from Xanthomonas campestris.,Yew WS, Fedorov AA, Fedorov EV, Rakus JF, Pierce RW, Almo SC, Gerlt JA Biochemistry. 2006 Dec 12;45(49):14582-97. PMID:17144652 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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