6UKD
Co-complex of S. pyogenes 10782 streptopain bound with a nitrile-based specific covalent inhibitor
Summary for 6UKD
| Entry DOI | 10.2210/pdb6ukd/pdb |
| Descriptor | Streptopain, benzyl [(2S)-1-(3-nitrophenyl)-3-oxobutan-2-yl]carbamate, NITRATE ION, ... (4 entities in total) |
| Functional Keywords | speb, streptopain, inhibitor, nitrile, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Streptococcus pyogenes ATCC 10782 |
| Total number of polymer chains | 1 |
| Total formula weight | 42018.30 |
| Authors | Wolan, D.W.,Woehl, J.L.,Kitamura, S. (deposition date: 2019-10-04, release date: 2020-09-09, Last modification date: 2024-11-20) |
| Primary citation | Woehl, J.L.,Kitamura, S.,Dillon, N.,Han, Z.,Edgar, L.J.,Nizet, V.,Wolan, D.W. An Irreversible Inhibitor to Probe the Role ofStreptococcus pyogenesCysteine Protease SpeB in Evasion of Host Complement Defenses. Acs Chem.Biol., 15:2060-2069, 2020 Cited by PubMed Abstract: Members of the CA class of cysteine proteases have multifaceted roles in physiology and virulence for many bacteria. Streptococcal pyrogenic exotoxin B (SpeB) is secreted by and implicated in the pathogenesis of the bacterium through degradation of key human immune effector proteins. Here, we developed and characterized a clickable inhibitor, , based on X-ray crystallographic analysis and structure-activity relationships. Our SpeB probe showed irreversible enzyme inhibition in biochemical assays and labeled endogenous SpeB in cultured supernatants. Importantly, application of decreased survival in the presence of human neutrophils and supports the role of SpeB-mediated proteolysis as a mechanism to limit complement-mediated host defense. We posit that our SpeB inhibitor will be a useful chemical tool to regulate, label, and quantitate secreted cysteine proteases with SpeB-like activity in complex biological samples and a lead candidate for new therapeutics designed to sensitize to host immune clearance. PubMed: 32662975DOI: 10.1021/acschembio.0c00191 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.589 Å) |
Structure validation
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