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| | <StructureSection load='6i9a' size='340' side='right'caption='[[6i9a]], [[Resolution|resolution]] 1.20Å' scene=''> | | <StructureSection load='6i9a' size='340' side='right'caption='[[6i9a]], [[Resolution|resolution]] 1.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6i9a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_33277 Atcc 33277]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I9A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I9A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6i9a]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Porphyromonas_gingivalis Porphyromonas gingivalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6I9A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6I9A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H8E:benzyl-N-[(2S)-1-[[(3S)-7-amino-1-(benzylamino)-1,2-dioxoheptan-3-yl]amino]-5-(2-methyl-2-phenylhydrazinyl)-1,5-dioxopentan-2-yl]carbamate'>H8E</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">kgp, prtK, prtP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=837 ATCC 33277])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DTV:(2S,3S)-1,4-DIMERCAPTOBUTANE-2,3-DIOL'>DTV</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=H8E:benzyl-N-[(2S)-1-[[(3S)-7-amino-1-(benzylamino)-1,2-dioxoheptan-3-yl]amino]-5-(2-methyl-2-phenylhydrazinyl)-1,5-dioxopentan-2-yl]carbamate'>H8E</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=UNX:UNKNOWN+ATOM+OR+ION'>UNX</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Gingipain_K Gingipain K], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.47 3.4.22.47] </span></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=6i9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9a OCA], [https://pdbe.org/6i9a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6i9a RCSB], [https://www.ebi.ac.uk/pdbsum/6i9a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9a ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6i9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i9a OCA], [http://pdbe.org/6i9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i9a RCSB], [http://www.ebi.ac.uk/pdbsum/6i9a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i9a ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KGP83_PORGN KGP83_PORGN]] Cysteine proteinase with a strong preference for substrates with Lys in the P1 position. Hydrolyzes bovine hemoglobin, bovine serum albumin, casein, human placental type I collagen and human IgA and IgG. Disrupts the functions of polymorphonuclear leukocytes. May act as a virulence factor in the development of peridontal disease. Involved in the coaggregation of P.gingivalis with other oral bacteria (By similarity).[UniProtKB:B2RLK2] | + | [https://www.uniprot.org/uniprot/KGP83_PORGN KGP83_PORGN] Cysteine proteinase with a strong preference for substrates with Lys in the P1 position. Hydrolyzes bovine hemoglobin, bovine serum albumin, casein, human placental type I collagen and human IgA and IgG. Disrupts the functions of polymorphonuclear leukocytes. May act as a virulence factor in the development of peridontal disease. Involved in the coaggregation of P.gingivalis with other oral bacteria (By similarity).[UniProtKB:B2RLK2] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6i9a" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6i9a" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Proteinase 3D structures|Proteinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 33277]] | |
| - | [[Category: Gingipain K]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gomis-Ruth, F X]] | + | [[Category: Porphyromonas gingivalis]] |
| - | [[Category: Guevara, T]] | + | [[Category: Gomis-Ruth FX]] |
| - | [[Category: Rofdriguez-Banqueri, A]] | + | [[Category: Guevara T]] |
| - | [[Category: Custeine peptidase]]
| + | [[Category: Rofdriguez-Banqueri A]] |
| - | [[Category: Gingipain]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Peptidase inhibitor]]
| + | |
| - | [[Category: Periodontal disease]]
| + | |
| - | [[Category: Periodontopathogen]]
| + | |
| - | [[Category: Porphyromonas gingivali]]
| + | |
| Structural highlights
6i9a is a 2 chain structure with sequence from Porphyromonas gingivalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.2Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
KGP83_PORGN Cysteine proteinase with a strong preference for substrates with Lys in the P1 position. Hydrolyzes bovine hemoglobin, bovine serum albumin, casein, human placental type I collagen and human IgA and IgG. Disrupts the functions of polymorphonuclear leukocytes. May act as a virulence factor in the development of peridontal disease. Involved in the coaggregation of P.gingivalis with other oral bacteria (By similarity).[UniProtKB:B2RLK2]
Publication Abstract from PubMed
Porphyromonas gingivalis is a member of the dysbiotic oral microbiome and a "keystone pathogen" that causes severe periodontal disease, which is among the most prevalent infectious diseases. Part of the virulence factors secreted by P. gingivalis are the essential cysteine peptidases gingipain K (Kgp) and R (RgpA and RgpB), which account for 85% of the extracellular proteolytic activity of the pathogen and are thus prime targets for inhibition. We report the high-resolution (1.20 A) complex structure of Kgp with KYT-36, a peptide-derived, potent, bioavailable and highly selective inhibitor, which is widely used for studies in vitro, in cells and in vivo. Sub-nanomolar inhibition of Kgp is achieved by tight binding to the active-site cleft, which is covered for its sub-sites S3 through S1' under establishment of nine hydrophobic interactions, 14 hydrogen bonds and one salt bridge. In addition, an inhibitor carbonyl carbon that mimics the scissile carbonyl of substrates is pyramidalized and just 2.02 A away from the catalytic nucleophile of Kgp, C(477)Sgamma. Thus, the crystal structure emulates a reaction intermediate of the first nucleophilic attack during catalysis of cysteine peptidases. The present study sets the pace for the development of tailored next-generation drugs to tackle P. gingivalis.
Structural determinants of inhibition of Porphyromonas gingivalis gingipain K by KYT-36, a potent, selective, and bioavailable peptidase inhibitor.,Guevara T, Rodriguez-Banqueri A, Lasica AM, Ksiazek M, Potempa BA, Potempa J, Gomis-Ruth FX Sci Rep. 2019 Mar 20;9(1):4935. doi: 10.1038/s41598-019-41354-3. PMID:30894633[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Guevara T, Rodriguez-Banqueri A, Lasica AM, Ksiazek M, Potempa BA, Potempa J, Gomis-Ruth FX. Structural determinants of inhibition of Porphyromonas gingivalis gingipain K by KYT-36, a potent, selective, and bioavailable peptidase inhibitor. Sci Rep. 2019 Mar 20;9(1):4935. doi: 10.1038/s41598-019-41354-3. PMID:30894633 doi:http://dx.doi.org/10.1038/s41598-019-41354-3
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