2014
DOI: 10.1074/jbc.m113.545293
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Mechanistic Investigations of Unsaturated Glucuronyl Hydrolase from Clostridium perfringens

Abstract: Background: Unsaturated glucuronyl hydrolases (UGL) from GH88 are bacterial enzymes involved in the degradation of glycosaminoglycans and are virulence factors. Results: Mechanistic data inconsistent with the currently accepted mechanism of UGL are presented. Conclusion: A revised mechanism is proposed to explain all mechanistic data published to date. Significance: Understanding of the mechanism of UGL may allow design of bacteriostatic agents.

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Cited by 8 publications
(15 citation statements)
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“…The discovery of GH105 enzymes, which are unsaturated uronyl hydrolases that cleave the 4,5-unsaturated residues from the nonreducing ends of PL-generated oligouronates (21,22), has hinted at the potential for an alternate model of pectin metabolism. The mechanism of GH105 catalysis is thought to parallel that of GH88 members, which results in release of the linearized monosaccharide directly (23,24). The direct release of DKI by GH105 enzymes would obviate the need for a PL22 (or potentially an equivalent) and KdgF to convert the unsaturated nonreducing ends of PL-generated oligouronates into DKI.…”
mentioning
confidence: 99%
“…The discovery of GH105 enzymes, which are unsaturated uronyl hydrolases that cleave the 4,5-unsaturated residues from the nonreducing ends of PL-generated oligouronates (21,22), has hinted at the potential for an alternate model of pectin metabolism. The mechanism of GH105 catalysis is thought to parallel that of GH88 members, which results in release of the linearized monosaccharide directly (23,24). The direct release of DKI by GH105 enzymes would obviate the need for a PL22 (or potentially an equivalent) and KdgF to convert the unsaturated nonreducing ends of PL-generated oligouronates into DKI.…”
mentioning
confidence: 99%
“…[14] Interestingly,this makes UGLs relatively promiscuous enzymes that are capable of accepting ar ange of substrates with different aglycones,s ince the aglycone is not directly involved in the rate determining step of this mechanism. [15,16] UGLs represent an excellent and challenging test case for design of screens for unconventional glycosidases.Firstly,they are relatively rare enzymes,w ith only 1449 entries in the GH88 family and 2562 entries in the GH105 family (compared to for example more than 12 000 entries in GH2, the family that contains most of the known b-glucuronidases). Secondly,a ss hown in the present study,t he conventional MU-glycoside screening substrates of UGLs are cleaved, albeit slowly,b yb-glucuronidases.S ince b-glucuronidase activity occurs much more frequently than UGL activity in metagenomic genes,s creening for UGL activity with MUglycosides of unsaturated glucuronides can lead to false positive hits that contain genes for b-glucuronidases and not UGLs.F urther,s ince our metagenomic libraries are expressed in the E. coli strain EPI300, b-glucuronidase from E. coli [17] (BGE) will always be present in the screening media, giving rise to ahigh background activity (although this could be avoided in future screens by using BGE deficient strains of E. coli).…”
mentioning
confidence: 99%
“…Moreover, these studies suggest that this is the rate‐determining step of this mechanism . Interestingly, this makes UGLs relatively promiscuous enzymes that are capable of accepting a range of substrates with different aglycones, since the aglycone is not directly involved in the rate determining step of this mechanism …”
Section: Figurementioning
confidence: 99%