9JXT
An aldehyde-containing intermediate of SufS in complex with (2R,3R)-3-ethoxycarbonylaziridine-2-carboxylic acid
This is a non-PDB format compatible entry.
Summary for 9JXT
| Entry DOI | 10.2210/pdb9jxt/pdb |
| Descriptor | Cysteine desulfurase SufS, DI(HYDROXYETHYL)ETHER, (2~{S})-2-[(~{E})-[2-methyl-3-oxidanyl-5-(phosphonooxymethyl)pyridin-4-yl]methylideneamino]-3-oxidanylidene-propanoic acid, ... (4 entities in total) |
| Functional Keywords | cysteine desulfurase, biosynthetic protein |
| Biological source | Bacillus subtilis subsp. subtilis str. 168 |
| Total number of polymer chains | 1 |
| Total formula weight | 47024.91 |
| Authors | Nakamura, R.,Fujishiro, T. (deposition date: 2024-10-11, release date: 2025-07-16, Last modification date: 2025-09-03) |
| Primary citation | Fujishiro, T.,Otsuka, H.,Nakamura, R.,Fujihara, T. Discovery of an Aziridine-Based Inhibitor That Targets Cysteine Desulfurase Type II SufS via High-Throughput X‐ray Crystallography. Acs Med.Chem.Lett., 16:1546-1553, 2025 Cited by PubMed Abstract: Structure-based drug design is an emerging technology for developing new drugs. However, in silico modeling and predicting inhibitors covalently bound to cofactor-containing enzymes remain challenging. Here, we demonstrate an alternative approach for visualizing protein inhibitor binding via X-ray crystallography of PLP-dependent enzyme crystals. Specifically, we used crystals of type II cysteine desulfurase, SufS, a drug-target enzyme in the iron-sulfur cluster biosynthetic SUF system. We identified (2,3)-3-ethoxycarbonylaziridine-2-carboxylic acid (EAC) as a selective inhibitor of SufS. The X-ray crystal structures of SufS soaked with EAC for 12 and 24 h showed PLP-ligand conjugates. Two PLP-ligand conjugate species were assigned to l-α-formylglycine-PLP external aldimine and aminomalonate-PLP external aldimine, which could be caused by the aziridine ring opening reaction, removal of the ethyl ester, and air oxidation. This strategy could help identify new drug candidates specific to SufS, a new drug target in pathogenic microorganisms containing iron-sulfur cluster biosynthetic SUF systems. PubMed: 40832543DOI: 10.1021/acsmedchemlett.5c00168 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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