6JTB
Crystal structure of dipeptidyl peptidase 11 (DPP11) with citrate from Porphyromonas gingivalis (Space)
Summary for 6JTB
| Entry DOI | 10.2210/pdb6jtb/pdb |
| Related | 4Y04 |
| Descriptor | Asp/Glu-specific dipeptidyl-peptidase, DI(HYDROXYETHYL)ETHER, CITRIC ACID, ... (6 entities in total) |
| Functional Keywords | dipeptidyl aminopeptidase, s46, perio, microgravity, antimicrobial, hydrolase |
| Biological source | Porphyromonas gingivalis (strain ATCC 33277 / DSM 20709 / CIP 103683 / JCM 12257 / NCTC 11834 / 2561) |
| Total number of polymer chains | 1 |
| Total formula weight | 83175.27 |
| Authors | Sakamoto, Y.,Suzuki, Y.,Iizuka, I.,Roppongi, S.,Kushibiki, C.,Nakamura, A.,Ogasawara, W.,Tanaka, N. (deposition date: 2019-04-10, release date: 2019-10-02, Last modification date: 2023-11-22) |
| Primary citation | Sakamoto, Y.,Suzuki, Y.,Nakamura, A.,Watanabe, Y.,Sekiya, M.,Roppongi, S.,Kushibiki, C.,Iizuka, I.,Tani, O.,Sakashita, H.,Inaka, K.,Tanaka, H.,Yamada, M.,Ohta, K.,Honma, N.,Shida, Y.,Ogasawara, W.,Nakanishi-Matsui, M.,Nonaka, T.,Gouda, H.,Tanaka, N. Fragment-based discovery of the first nonpeptidyl inhibitor of an S46 family peptidase. Sci Rep, 9:13587-13587, 2019 Cited by PubMed Abstract: Antimicrobial resistance is a global public threat and raises the need for development of new antibiotics with a novel mode of action. The dipeptidyl peptidase 11 from Porphyromonas gingivalis (PgDPP11) belongs to a new class of serine peptidases, family S46. Because S46 peptidases are not found in mammals, these enzymes are attractive targets for novel antibiotics. However, potent and selective inhibitors of these peptidases have not been developed to date. In this study, a high-resolution crystal structure analysis of PgDPP11 using a space-grown crystal enabled us to identify the binding of citrate ion, which could be regarded as a lead fragment mimicking the binding of a substrate peptide with acidic amino acids, in the S1 subsite. The citrate-based pharmacophore was utilized for in silico inhibitor screening. The screening resulted in an active compound SH-5, the first nonpeptidyl inhibitor of S46 peptidases. SH-5 and a lipophilic analog of SH-5 showed a dose-dependent inhibitory effect against the growth of P. gingivalis. The binding mode of SH-5 was confirmed by crystal structure analysis. Thus, these compounds could be lead structures for the development of selective inhibitors of PgDPP11. PubMed: 31537874DOI: 10.1038/s41598-019-49984-3 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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