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[[Image:2brp.gif|left|200px]]
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{{STRUCTURE_2brp|  PDB=2brp  |  SCENE=  }}
'''CRYSTAL STRUCTURE OF S.PNEUMONIAE HYALURONATE LYASE IN COMPLEX WITH W249B'''


==Crystal structure of S. pneumoniae hyaluronate lyase in complex with W249b==
<StructureSection load='2brp' size='340' side='right'caption='[[2brp]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2brp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BRP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BRP 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]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SIE:SULFAMIC+ACID+1-DECYL-2-(4-SULFAMOYLOXYPHENYL)-1H-INDOL-6-YL+ESTER'>SIE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XLS:D-XYLOSE+(LINEAR+FORM)'>XLS</scene></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=2brp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2brp OCA], [https://pdbe.org/2brp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2brp RCSB], [https://www.ebi.ac.uk/pdbsum/2brp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2brp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HYSA_STRPN HYSA_STRPN]
== 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/br/2brp_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=2brp ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The bacterial hyaluronan lyases (Hyals) that degrade hyaluronan, an important component of the extracellular matrix, are involved in microbial spread. Inhibitors of these enzymes are essential in investigation of the role of hyaluronan and Hyal in bacterial infections and constitute a new class of antibiotics against Hyal-producing bacteria. Recently, we identified 1,3-diacetylbenzimidazole-2-thione and related molecules as inhibitors of streptococcal Hyal. One of such compounds, 1-decyl-2-(4-sulfamoyloxyphenyl)-1-indol-6-yl sulfamate, was co-crystallized in a complex with Streptococcus pneumoniae Hyal and its structure elucidated. The resultant X-ray structure demonstrates that this inhibitor fits in the enzymatic active site via interactions resembling the binding mode of the natural hyaluronan substrate. X-ray structural analysis also indicates binding interactions with the catalytic residues and those of a catalytically essential hydrophobic patch. An IC50 value of 11 microM for Hyal from Streptococcus agalactiae (strain 4755) qualifies this phenylindole compound as one of the most potent Hyal inhibitors known to date. The structural data suggested a similar binding mode for N-(3-phenylpropionyl)-benzoxazole-2-thione. This new compound's inhibitory properties were confirmed resulting in discovery of yet another Hyal inhibitor (IC50 of 15 microM). These benzoxazole-2-thiones constitute a new class of inhibitors of bacterial Hyals and are well suited for further optimization of their selectivity, potency, and pharmacokinetic properties.


==Overview==
Design of new benzoxazole-2-thione-derived inhibitors of Streptococcus pneumoniae hyaluronan lyase: structure of a complex with a 2-phenylindole.,Rigden DJ, Botzki A, Nukui M, Mewbourne RB, Lamani E, Braun S, von Angerer E, Bernhardt G, Dove S, Buschauer A, Jedrzejas MJ Glycobiology. 2006 Aug;16(8):757-65. Epub 2006 Apr 25. PMID:16638841<ref>PMID:16638841</ref>
The bacterial hyaluronan lyases (Hyals) that degrade hyaluronan, an important component of the extracellular matrix, are involved in microbial spread. Inhibitors of these enzymes are essential in investigation of the role of hyaluronan and Hyal in bacterial infections and constitute a new class of antibiotics against Hyal-producing bacteria. Recently, we identified 1,3-diacetylbenzimidazole-2-thione and related molecules as inhibitors of streptococcal Hyal. One of such compounds, 1-decyl-2-(4-sulfamoyloxyphenyl)-1-indol-6-yl sulfamate, was co-crystallized in a complex with Streptococcus pneumoniae Hyal and its structure elucidated. The resultant X-ray structure demonstrates that this inhibitor fits in the enzymatic active site via interactions resembling the binding mode of the natural hyaluronan substrate. X-ray structural analysis also indicates binding interactions with the catalytic residues and those of a catalytically essential hydrophobic patch. An IC50 value of 11 microM for Hyal from Streptococcus agalactiae (strain 4755) qualifies this phenylindole compound as one of the most potent Hyal inhibitors known to date. The structural data suggested a similar binding mode for N-(3-phenylpropionyl)-benzoxazole-2-thione. This new compound's inhibitory properties were confirmed resulting in discovery of yet another Hyal inhibitor (IC50 of 15 microM). These benzoxazole-2-thiones constitute a new class of inhibitors of bacterial Hyals and are well suited for further optimization of their selectivity, potency, and pharmacokinetic properties.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2BRP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BRP OCA].
</div>
<div class="pdbe-citations 2brp" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Design of new benzoxazole-2-thione-derived inhibitors of Streptococcus pneumoniae hyaluronan lyase: structure of a complex with a 2-phenylindole., Rigden DJ, Botzki A, Nukui M, Mewbourne RB, Lamani E, Braun S, von Angerer E, Bernhardt G, Dove S, Buschauer A, Jedrzejas MJ, Glycobiology. 2006 Aug;16(8):757-65. Epub 2006 Apr 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16638841 16638841]
*[[Hyaluronidase 3D structures|Hyaluronidase 3D structures]]
[[Category: Hyaluronate lyase]]
== References ==
[[Category: Single protein]]
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus pneumoniae]]
[[Category: Streptococcus pneumoniae]]
[[Category: Jedrzejas, M J.]]
[[Category: Jedrzejas MJ]]
[[Category: Rigden, D J.]]
[[Category: Rigden DJ]]
[[Category: Lyase]]
[[Category: Peptidoglycan-anchor]]
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