1cvr: Difference between revisions

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CRYSTAL STRUCTURE OF THE ARG SPECIFIC CYSTEINE PROTEINASE GINGIPAIN R (RGPB)

OverviewOverview

Gingipains are cysteine proteinases acting as key virulence factors of the bacterium Porphyromonas gingivalis, the major pathogen in periodontal disease. The 1.5 and 2.0 A crystal structures of free and D-Phe-Phe-Arg-chloromethylketone-inhibited gingipain R reveal a 435-residue, single-polypeptide chain organized into a catalytic and an immunoglobulin-like domain. The catalytic domain is subdivided into two subdomains comprising four- and six-stranded beta-sheets sandwiched by alpha-helices. Each subdomain bears topological similarities to the p20-p10 heterodimer of caspase-1. The second subdomain harbours the Cys-His catalytic diad and a nearby Glu arranged around the S1 specificity pocket, which carries an Asp residue to enforce preference for Arg-P1 residues. This gingipain R structure is an excellent template for the rational design of drugs with a potential to cure and prevent periodontitis. Here we show the binding mode of an arginine-containing inhibitor in the active-site, thus identifying major interaction sites defining a suitable pharmacophor.

About this StructureAbout this Structure

1CVR is a Single protein structure of sequence from Porphyromonas gingivalis with and as ligands. Active as Gingipain R, with EC number 3.4.22.37 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of gingipain R: an Arg-specific bacterial cysteine proteinase with a caspase-like fold., Eichinger A, Beisel HG, Jacob U, Huber R, Medrano FJ, Banbula A, Potempa J, Travis J, Bode W, EMBO J. 1999 Oct 15;18(20):5453-62. PMID:10523290

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OCA

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-[[Image:1cvr.gif|left|200px]]<br /><applet load="1cvr" size="450" color="white" frame="true" align="right" spinBox="true"
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 caption="1cvr, resolution 2.0&Aring;" />
 '''CRYSTAL STRUCTURE OF THE ARG SPECIFIC CYSTEINE PROTEINASE GINGIPAIN R (RGPB)'''<br />
 ==Overview==
-Gingipains are cysteine proteinases acting as key virulence factors of the, bacterium Porphyromonas gingivalis, the major pathogen in periodontal, disease. The 1.5 and 2.0 A crystal structures of free and, D-Phe-Phe-Arg-chloromethylketone-inhibited gingipain R reveal a, 435-residue, single-polypeptide chain organized into a catalytic and an, immunoglobulin-like domain. The catalytic domain is subdivided into two, subdomains comprising four- and six-stranded beta-sheets sandwiched by, alpha-helices. Each subdomain bears topological similarities to the, p20-p10 heterodimer of caspase-1. The second subdomain harbours the, Cys-His catalytic diad and a nearby Glu arranged around the S1 specificity, pocket, which carries an Asp residue to enforce preference for Arg-P1, residues. This gingipain R structure is an excellent template for the, rational design of drugs with a potential to cure and prevent, periodontitis. Here we show the binding mode of an arginine-containing, inhibitor in the active-site, thus identifying major interaction sites, defining a suitable pharmacophor.
+Gingipains are cysteine proteinases acting as key virulence factors of the bacterium Porphyromonas gingivalis, the major pathogen in periodontal disease. The 1.5 and 2.0 A crystal structures of free and D-Phe-Phe-Arg-chloromethylketone-inhibited gingipain R reveal a 435-residue, single-polypeptide chain organized into a catalytic and an immunoglobulin-like domain. The catalytic domain is subdivided into two subdomains comprising four- and six-stranded beta-sheets sandwiched by alpha-helices. Each subdomain bears topological similarities to the p20-p10 heterodimer of caspase-1. The second subdomain harbours the Cys-His catalytic diad and a nearby Glu arranged around the S1 specificity pocket, which carries an Asp residue to enforce preference for Arg-P1 residues. This gingipain R structure is an excellent template for the rational design of drugs with a potential to cure and prevent periodontitis. Here we show the binding mode of an arginine-containing inhibitor in the active-site, thus identifying major interaction sites defining a suitable pharmacophor.
 ==About this Structure==
-CVR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Porphyromonas_gingivalis Porphyromonas gingivalis] with CA and ZN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Gingipain_R Gingipain R], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.37 3.4.22.37] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1CVR OCA].
+CVR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Porphyromonas_gingivalis Porphyromonas gingivalis] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Gingipain_R Gingipain R], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.37 3.4.22.37] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CVR OCA].
 ==Reference==
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 [[Category: Porphyromonas gingivalis]]
 [[Category: Single protein]]
-[[Category: Beisel, H.G.]]
+[[Category: Beisel, H G.]]
 [[Category: Eichinger, A.]]
 [[Category: CA]]
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 [[Category: cysteine proteinase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 12:47:32 2007''
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