2Y6T

Molecular Recognition of Chymotrypsin by the Serine Protease Inhibitor Ecotin from Yersinia pestis

Summary for 2Y6T

• Entry DOI: 10.2210/pdb2y6t/pdb
• Related: 1AB9 1ACB 1AFQ 1CA0 1CBW 1CGI 1CGJ 1CHG 1CHO 1DLK 1EX3 1GCD 1GCT 1GG6 1GGD 1GHA 1GHB 1GL0 1GL1 1GMC 1GMD 1GMH 1HJA 1K2I 1MTN 1N8O 1OXG 1P2M 1P2N 1P2O 1P2Q 1T7C 1T8L 1T8M 1T8N 1T8O 1VGC 1YPH 2CGA 2CHA 2GCH 2GCT 2GMT 2VGC 3GCH 3GCT 3VGC 4CHA 4GCH 4VGC 5CHA 5GCH 6CHA 6GCH 7GCH 8GCH
• Descriptor: CHYMOTRYPSINOGEN A, ECOTIN, SULFATE ION, ... (4 entities in total)
• Functional Keywords: hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: YERSINIA PSEUDOTUBERCULOSIS; More
• Cellular location: Secreted, extracellular space: P00766; Periplasm : B1JSA0
• Total number of polymer chains: 8
• Total formula weight: 170117.12

Authors

Clark, E.A.,Walker, N.,Ford, D.C.,Cooper, I.A.,Oyston, P.C.F.,Acharya, K.R. (deposition date: 2011-01-26, release date: 2011-04-20, Last modification date: 2024-11-20)

Primary citation

Clark, E.A.,Walker, N.,Ford, D.C.,Cooper, I.A.,Oyston, P.C.,Acharya, K.R.
Molecular Recognition of Chymotrypsin by the Serine Protease Inhibitor Ecotin from Yersinia Pestis.
J.Biol.Chem., 286:24015-, 2011

PubMed Abstract: Resistance to antibiotics is a problem not only in terms of healthcare but also biodefense. Engineering of resistance into a human pathogen could create an untreatable biothreat pathogen. One such pathogen is Yersinia pestis, the causative agent of plague. Previously, we have used a bioinformatic approach to identify proteins that may be suitable targets for antimicrobial therapy and in particular for the treatment of plague. The serine protease inhibitor ecotin was identified as one such target. We have carried out mutational analyses in the closely related Yersinia pseudotuberculosis, validating that the ecotin gene is a virulence-associated gene in this bacterium. Y. pestis ecotin inhibits chymotrypsin. Here, we present the structure of ecotin in complex with chymotrypsin to 2.74 Å resolution. The structure features a biologically relevant tetramer whereby an ecotin dimer binds to two chymotrypsin molecules, similar to what was observed in related serine protease inhibitor structures. However, the vast majority of the interactions in the present structure are distinctive, indicating that the broad specificity of the inhibitor for these proteases is based largely on its capacity to recognize features unique to each of them. These findings will have implications for the development of small ecotin inhibitors for therapeutic use.

PubMed: 21531711
DOI: 10.1074/JBC.M111.225730

Experimental method

X-RAY DIFFRACTION (2.74 Å)