Structural highlights
5a59 is a 1 chain structure with sequence from Streptococcus pneumoniae TIGR4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | X-ray diffraction, Resolution 2.5Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
GH101_STRPN Is involved in the breakdown of mucin-type O-linked glycans. Specifically removes the T-antigen disaccharide (Gal-beta-1,3-GalNAc-alpha) from extracellular host glycoproteins. Is representative of a broadly important class of virulence factors (By similarity).
Publication Abstract from PubMed
O-linked glycosylation is one of the most abundant post-translational modifications of proteins. Within the secretory pathway of higher eukaryotes, the core of these glycans is frequently an N-acetylgalactosamine residue that is alpha-linked to serine or threonine residues. Glycoside hydrolases in family 101 are presently the only known enzymes to be able to hydrolyze this glycosidic linkage. Here we determine the high-resolution structures of the catalytic domain comprising a fragment of GH101 from Streptococcus pneumoniae TIGR4, SpGH101, in the absence of carbohydrate, and in complex with reaction products, inhibitor, and substrate analogues. Upon substrate binding, a tryptophan lid (residues 724-WNW-726) closes on the substrate. The closing of this lid fully engages the substrate in the active site with D764 positioned directly beneath C1 of the sugar residue bound within the -1 subsite, consistent with its proposed role as the catalytic nucleophile. In all of the bound forms of the enzyme, however, the proposed catalytic acid/base residue was found to be too distant from the glycosidic oxygen (>4.3 A) to serve directly as a general catalytic acid/base residue and thereby facilitate cleavage of the glycosidic bond. These same complexes, however, revealed a structurally conserved water molecule positioned between the catalytic acid/base and the glycosidic oxygen. On the basis of these structural observations we propose a new variation of the retaining glycoside hydrolase mechanism wherein the intervening water molecule enables a Grotthuss proton shuttle between E796 and the glycosidic oxygen, permitting this residue to serve as the general acid/base catalytic residue.
Structural analysis of a family 101 glycoside hydrolase in complex with carbohydrates reveals insights into its mechanism.,Gregg KJ, Suits MD, Deng L, Vocadlo DJ, Boraston AB J Biol Chem. 2015 Aug 24. pii: jbc.M115.680470. PMID:26304114[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gregg KJ, Suits MD, Deng L, Vocadlo DJ, Boraston AB. Structural analysis of a family 101 glycoside hydrolase in complex with carbohydrates reveals insights into its mechanism. J Biol Chem. 2015 Aug 24. pii: jbc.M115.680470. PMID:26304114 doi:http://dx.doi.org/10.1074/jbc.M115.680470
