Structure of the Mature Streptococcal Cysteine Protease Exotoxin mSpeB in Its Active Dimeric Form

Olsen, Johan G. (author)

Dagil, Robert (author)

Niclasen, Louise Meinert (author)

Sørensen, Ole E (author): Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine

Kragelund, Birthe B. (author)

(creator_code:org_t)

Elsevier BV, 2009
2009
English.
In: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 393:3, s. 693-703

Related links:: http://dx.doi.org/10...; show more...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Abstract Subject headings

Invasive infections of Streptococcus pyogenes are dependent on the cysteine protease streptococcal pyrogenic exotoxin B. Previous structures of the enzyme have not disclosed the proper active-site configuration. Here, the crystal structure of the mature enzyme is presented to 1.55 angstrom, disclosing a homodimer. A serine from one subunit inserts into the active site of the other to donate to the oxyanion hole and coordinates the ligand proximal to the active-site cysteine. Dimerization. is unique to the mature form and is clearly a prerequisite for catalysis. The present structure supports a tripartite switch system that is triggered upon dimerization and substrate binding: (1) liberation of the active-site histidine from an inactive configuration, (2) relocation of residues blocking the substrate binding pockets and (3) repositioning of two active-site tryptophans to settle in the active configuration. Based on the present structure, the active site of clan CA cysteine proteases is expanded and a detailed mechanism of the deacylation mechanism is proposed. The results may have applications for the development of protease inhibitors specific to bacterial cysteine proteases. (c) 2009 Elsevier Ltd. All rights reserved.

By the author/editor: Olsen, Johan G.; Dagil, Robert; Niclasen, Louise ...; Sørensen, Ole E; Kragelund, Birth ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Infectious Medic ...

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