2brp
From Proteopedia
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| - | [[Image:2brp.gif|left|200px]] | + | [[Image:2brp.gif|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF S.PNEUMONIAE HYALURONATE LYASE IN COMPLEX WITH W249B''' | + | {{Structure |
| + | |PDB= 2brp |SIZE=350|CAPTION= <scene name='initialview01'>2brp</scene>, resolution 2.00Å | ||
| + | |SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene> | ||
| + | |LIGAND= <scene name='pdbligand=XLS:D-XYLOSE+(LINEAR+FORM)'>XLS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=SIE:SULFAMIC ACID 1-DECYL-2-(4-SULFAMOYLOXYPHENYL)-1H-INDOL-6-YL ESTER'>SIE</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Hyaluronate_lyase Hyaluronate lyase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.2.1 4.2.2.1] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF S.PNEUMONIAE HYALURONATE LYASE IN COMPLEX WITH W249B''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2BRP is a [ | + | 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]. |
==Reference== | ==Reference== | ||
| - | 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:// | + | 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] |
[[Category: Hyaluronate lyase]] | [[Category: Hyaluronate lyase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: peptidoglycan-anchor]] | [[Category: peptidoglycan-anchor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:05:51 2008'' |
Revision as of 14:05, 20 March 2008
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| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , and | ||||||
| Activity: | Hyaluronate lyase, with EC number 4.2.2.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF S.PNEUMONIAE HYALURONATE LYASE IN COMPLEX WITH W249B
Overview
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
2BRP is a Single protein structure of sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA.
Reference
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
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