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Catalytic Site Atlas

CSA LITERATURE entry for 1qaz

E.C. name
SpeciesSphingomonas sp. ()
E.C. Number (IntEnz) 3.5.1.45
CSA Homologues of 1qaz1hv6,3evh,3evl,3ew4,
CSA Entries With UniProtID
CSA Entries With EC Number 3.5.1.45
PDBe Entry 1qaz
PDBSum Entry 1qaz
MACiE Entry 1qaz

Literature Report

IntroductionThe enzyme alginate lyase from the bacteria Sphingomonas sp. is able to degrade the polymer alginate by eliminative cleavage. Alginate is made up of beta-d-mannuronate and beta-d-glucoronate linked together by a beta-1-4 glycosidic linkage, and alginate lyase is able to cleave this linkage to release two oligosaccharides. The enzyme may have potential therapeutic applications because one of the symptoms of cystic fibrosis is a thick layer of alginate that builds up inside the lungs making breathing difficult. The bacterial species produces three types of Alginate lyase, which are non-homologous but display similar organisation in the active site, suggesting that convergent evolution may account for their similar functions. Here, the structure and mechanism of Alginate lyase III is described.
MechansimThe alginate substrate is cleaved by elimination. To this end, Tyr 246 acts as a base for deprotonation of the mannuronate moiety at C5 resulting in a carbanion whose negative charge can be delocalised through the carboxylate group and is stabilised by Arg 239 and Asn 191. Arg 239 also acts to lower the pKa of Tyr 246 so that more molecules are in the ionised state at physiological pH. The bridging oxygen is then protonated by Tyr 246 to allow the cleavage of the glycosidic bond, resulting in the formation of a C4-C5 double bond. This releases the two oligosaccharide products.
Reaction

Catalytic Sites for 1qaz

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
TyrA246294macie:sideChainActs as general base to deprotonate the 5 carbon. Then acts as general acid to protonate the bridging oxygen, allowing cleavage of the glycosidic bond.
AsnA191239macie:sideChainStabilises the carbanion transition state through electrostatic contacts.
ArgA239287macie:sideChainStabilises the carbanion intermediate through electrostatic contacts. Also acts to lower the pKa of Tyr 246 thus allowing it to act as a base at physiological pH.

Literature References

Notes:
Yoon HJ
Crystal structure of alginate lyase A1-III complexed with trisaccharide product at 2.0 A resolution.
J Mol Biol 2001 307 9-16
PubMed: 11243798
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