View source for 3anj


==Crystal structure of unsaturated glucuronyl hydrolase from Streptcoccus agalactiae==
<StructureSection load='3anj' size='340' side='right'caption='[[3anj]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3anj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_agalactiae_serogroup_III Streptococcus agalactiae serogroup III]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ANJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ANJ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3anj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3anj OCA], [https://pdbe.org/3anj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3anj RCSB], [https://www.ebi.ac.uk/pdbsum/3anj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3anj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UCDH_STRA3 UCDH_STRA3] Catalyzes the hydrolysis of unsaturated hyaluronate and chondroitin disaccharides. Also degrades unsaturated heparin disaccharides. Releases 4-deoxy-4,5-didehydro D-glucuronic acid or 4-deoxy-4,5-didehydro L-iduronic acid from chondroitin disaccharides, hyaluronan disaccharides and heparin disaccharides and cleaves both glycosidic (1->3) and (1->4) bonds. Prefers sulfated glycosaminoglycans compared to unsulfated glycosaminoglycans. Probably required for mammalian cells invasion through the degradation of extracellular sulfated glycosaminoglycans such as chondroitin and hyaluronan.<ref>PMID:19416976</ref> <ref>PMID:21147778</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/an/3anj_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3anj ConSurf].
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== Publication Abstract from PubMed ==
Pathogenic Streptococcus agalactiae produces polysaccharide lyases and unsaturated glucuronyl hydrolase (UGL), which are prerequisite for complete degradation of mammalian extracellular matrices, including glycosaminoglycans such as chondroitin and hyaluronan. Unlike the Bacillus enzyme, streptococcal UGLs prefer sulfated glycosaminoglycans. Here, we show the loop flexibility for substrate binding and structural determinants for recognition of glycosaminoglycan sulfate groups in S. agalactiae UGL (SagUGL). UGL also degraded unsaturated heparin disaccharides; this indicates that the enzyme released unsaturated iduronic and glucuronic acids from substrates. We determined the crystal structures of SagUGL wild-type enzyme and both substrate-free and substrate-bound D175N mutants by x-ray crystallography and noted that the loop over the active cleft exhibits flexible motion for substrate binding. Several residues in the active cleft bind to the substrate, unsaturated chondroitin disaccharide with a sulfate group at the C-6 position of GalNAc residue. The sulfate group is hydrogen-bonded to Ser-365 and Ser-368 and close to Lys-370. As compared with wild-type enzyme, S365H, S368G, and K370I mutants exhibited higher Michaelis constants toward the substrate. The conversion of SagUGL to Bacillus sp. GL1 UGL-like enzyme via site-directed mutagenesis demonstrated that Ser-365 and Lys-370 are essential for direct binding and for electrostatic interaction, respectively, for recognition of the sulfate group by SagUGL. Molecular conversion was also achieved in SagUGL Arg-236 with an affinity for the sulfate group at the C-4 position of the GalNAc residue. These residues binding to sulfate groups are frequently conserved in pathogenic bacterial UGLs, suggesting that the motif "R-//-SXX(S)XK" (where the hyphen and slash marks in the motif indicate the presence of over 100 residues in the enzyme and parentheses indicate that Ser-368 makes little contribution to enzyme activity) is crucial for degradation of sulfated glycosaminoglycans.

Structural determinants in streptococcal unsaturated glucuronyl hydrolase for recognition of glycosaminoglycan sulfate groups.,Nakamichi Y, Maruyama Y, Mikami B, Hashimoto W, Murata K J Biol Chem. 2011 Feb 25;286(8):6262-71. Epub 2010 Dec 8. PMID:21147778<ref>PMID:21147778</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus agalactiae serogroup III]]
[[Category: Hashimoto W]]
[[Category: Maruyama Y]]
[[Category: Mikami B]]
[[Category: Murata K]]
[[Category: Nakamichi Y]]