6TCX

Papain bound to a natural cysteine protease inhibitor from Streptomyces mobaraensis

これはPDB形式変換不可エントリーです。

6TCX の概要

• エントリーDOI: 10.2210/pdb6tcx/pdb
• 分子名称: 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)
• 機能のキーワード: peptide inhibitor, cysteine protease, papain, structural genomics consortium, sgc, hydrolase
• 由来する生物種: Carica papaya (Papaya)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24302.29

構造登録者

Kraemer, A.,Juettner, N.E.,Fuchsbauer, H.-L.,Edwards, A.M.,Arrowsmith, C.H.,Bountra, C.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2019-11-06, 公開日: 2019-12-04, 最終更新日: 2024-10-09)

主引用文献

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

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: 32998509
DOI: 10.1021/acs.jnatprod.0c00201

実験手法

X-RAY DIFFRACTION (1.65 Å)