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| | ==Porphyromonas gingivalis gingipain K (Kgp) catalytic and immunoglobulin superfamily-like domains== | | ==Porphyromonas gingivalis gingipain K (Kgp) catalytic and immunoglobulin superfamily-like domains== |
| - | <StructureSection load='4rbm' size='340' side='right' caption='[[4rbm]], [[Resolution|resolution]] 1.75Å' scene=''> | + | <StructureSection load='4rbm' size='340' side='right'caption='[[4rbm]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4rbm]] is a 1 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=4RBM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RBM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4rbm]] is a 1 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=4RBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RBM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=AZI:AZIDE+ION'>AZI</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CKC:(3S)-3,7-DIAMINOHEPTAN-2-ONE'>CKC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HIS:HISTIDINE'>HIS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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]] 1.75Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ief|4ief]], [[1cvr|1cvr]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=AZI:AZIDE+ION'>AZI</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CKC:(3S)-3,7-DIAMINOHEPTAN-2-ONE'>CKC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HIS:HISTIDINE'>HIS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4rbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rbm OCA], [https://pdbe.org/4rbm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rbm RCSB], [https://www.ebi.ac.uk/pdbsum/4rbm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rbm ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rbm OCA], [http://pdbe.org/4rbm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rbm RCSB], [http://www.ebi.ac.uk/pdbsum/4rbm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rbm 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 4rbm" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4rbm" 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: Large Structures]] |
| - | [[Category: Gingipain K]] | + | [[Category: Porphyromonas gingivalis]] |
| - | [[Category: Diego, I de]]
| + | [[Category: Gomis-Ruth FX]] |
| - | [[Category: Gomis-Ruth, F X]] | + | [[Category: Guevara T]] |
| - | [[Category: Guevara, T]] | + | [[Category: Huntington JA]] |
| - | [[Category: Huntington, J A]] | + | [[Category: Pomowski A]] |
| - | [[Category: Pomowski, A]] | + | [[Category: Potempa B]] |
| - | [[Category: Potempa, B]] | + | [[Category: Potempa J]] |
| - | [[Category: Potempa, J]] | + | [[Category: Sztukowska MN]] |
| - | [[Category: Sztukowska, M N]] | + | [[Category: Veillard F]] |
| - | [[Category: Veillard, F]] | + | [[Category: De Diego I]] |
| - | [[Category: Alpha/beta-hydrolase]] | + | |
| - | [[Category: Cysteine peptidase]]
| + | |
| - | [[Category: Extracellular]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lysine-containing substrate]]
| + | |
| - | [[Category: Secreted]]
| + | |
| Structural highlights
4rbm is a 1 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 1.75Å |
| 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
Cysteine peptidases are key proteolytic virulence factors of the periodontopathogen Porphyromonas gingivalis, which causes chronic periodontitis, the most prevalent dysbiosis-driven disease in humans. Two peptidases, gingipain K (Kgp) and R (RgpA and RgpB), which differ in their selectivity after lysines and arginines, respectively, collectively account for 85% of the extracellular proteolytic activity of P. gingivalis at the site of infection. Therefore, they are promising targets for the design of specific inhibitors. While the structure of mature RgpB is known, little is known about Kgp, which shares only 27% sequence identity. We report the high-resolution crystal structure of a competent fragment of Kgp encompassing the catalytic cysteine peptidase domain and a downstream immunoglobulin superfamily-like domain, which is required for folding and secretion of Kgp in vivo. The structure, which strikingly resembles a tooth, was serendipitously trapped with a fragment of a covalent inhibitor targeting the catalytic cysteine. This provided accurate insight into the active site and suggested that catalysis may require a catalytic triad, C477-H444-D388, rather than the cysteine-histidine dyad normally found in cysteine peptidases. In addition, a 20A-long solvent-filled interior channel traverses the molecule and links the bottom of the specificity pocket with the molecular surface opposite the active-site cleft. This channel, absent in RgpB, may enhance the plasticity of the enzyme, which would explain the much lower activity in vitro towards comparable specific synthetic substrates. Overall, the present results report the architecture and molecular determinants of the working mechanism of Kgp, including interaction with its substrates.
Structure and mechanism of cysteine peptidase Kgp, a major virulence factor of Porphyromonas gingivalis in periodontitis.,de Diego I, Veillard F, Sztukowska M, Guevara T, Potempa B, Pomowski A, Huntington JA, Potempa J, Gomis-Ruth FX J Biol Chem. 2014 Sep 29. pii: jbc.M114.602052. PMID:25266723[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ de Diego I, Veillard F, Sztukowska M, Guevara T, Potempa B, Pomowski A, Huntington JA, Potempa J, Gomis-Ruth FX. Structure and mechanism of cysteine peptidase Kgp, a major virulence factor of Porphyromonas gingivalis in periodontitis. J Biol Chem. 2014 Sep 29. pii: jbc.M114.602052. PMID:25266723 doi:http://dx.doi.org/10.1074/jbc.M114.602052
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