6i9a | pdb_00006i9a

Porphyromonas gingivalis gingipain K (Kgp) in complex with inhibitor KYT-36

spinqualitylabelsall models 6i9a, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D 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: CA, DTV, EPE, GOL, H8E, NA, UNX 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Proteinase 3D structures

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