6TCX
Papain bound to a natural cysteine protease inhibitor from Streptomyces mobaraensis
This is a non-PDB format compatible entry.
Summary for 6TCX
| Entry DOI | 10.2210/pdb6tcx/pdb |
| Descriptor | Papain, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, (2~{R})-2-[[(1~{S})-1-[(6~{S})-2-azanyl-1,4,5,6-tetrahydropyrimidin-6-yl]-2-[[(2~{S})-3-methyl-1-oxidanylidene-1-[[(2~{S})-1-oxidanyl-3-phenyl-propan-2-yl]amino]butan-2-yl]amino]-2-oxidanylidene-ethyl]carbamoylamino]-3-(4-hydroxyphenyl)propanoic acid, ... (4 entities in total) |
| Functional Keywords | peptide inhibitor, cysteine protease, papain, structural genomics consortium, sgc, hydrolase |
| Biological source | Carica papaya (Papaya) |
| Total number of polymer chains | 1 |
| Total formula weight | 24302.29 |
| Authors | Kraemer, A.,Juettner, N.E.,Fuchsbauer, H.-L.,Edwards, A.M.,Arrowsmith, C.H.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2019-11-06, release date: 2019-12-04, Last modification date: 2024-10-09) |
| Primary citation | Juettner, N.E.,Bogen, J.P.,Bauer, T.A.,Knapp, S.,Pfeifer, F.,Huettenhain, S.H.,Meusinger, R.,Kraemer, A.,Fuchsbauer, H.L. Decoding the Papain Inhibitor from Streptomyces mobaraensis as Being Hydroxylated Chymostatin Derivatives: Purification, Structure Analysis, and Putative Biosynthetic Pathway. J.Nat.Prod., 83:2983-2995, 2020 Cited by PubMed Abstract: produces the papain inhibitor SPI consisting of a 12 kDa protein and small active compounds (SPI). Purification of the papain inhibitory compounds resulted in four diverse chymostatin derivatives that were characterized by NMR and MS analysis. Chymostatins are hydrophobic tetrapeptide aldehydes from streptomycetes, e.g., and , that reverse chymosin-mediated angiotensin activation and inhibit other serine and cysteine proteases. Chymotrypsin and papain were both inhibited by the SPI compounds in the low nanomolar range. SPI differs from the characterized chymostatins by the exchange of phenylalanine for tyrosine. The crystal structure of one of these chymostatin variants confirmed its molecular structure and revealed a S-configured hemithioacetal bond with the catalytic Cys25 thiolate as well as close interactions with hydrophobic S1 and S2 subsite amino acids. A model for chymostatin biosynthesis is provided based on the discovery of clustered genes encoding several putative nonribosomal peptide synthetases; among them, there is the unusual CstF enzyme that accommodates two canonical amino acid activation domains as well as three peptide carrier protein domains. PubMed: 32998509DOI: 10.1021/acs.jnatprod.0c00201 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
Download full validation report
