6XZX

crystal structure of human carbonic anhydrase I in complex with 4-(3-(2-((2-fluorobenzyl)amino)ethyl)ureido) benzenesulfonamide

Summary for 6XZX

• Entry DOI: 10.2210/pdb6xzx/pdb
• Related: 6xze 6xzo 6xzs
• Descriptor: Carbonic anhydrase 1, ZINC ION, 1-[2-[(phenylmethyl)amino]ethyl]-3-(3-sulfamoylphenyl)urea, ... (4 entities in total)
• Functional Keywords: inhibitor, carbon dioxide, carbonic anhydrase, lyase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 58640.03

Authors

Zanotti, G.,Majid, A.,Bozdag, M.,Angeli, A.,Carta, F.,Berto, P.,Supuran, C. (deposition date: 2020-02-05, release date: 2020-09-23, Last modification date: 2024-01-24)

Primary citation

Ali, M.,Bozdag, M.,Farooq, U.,Angeli, A.,Carta, F.,Berto, P.,Zanotti, G.,Supuran, C.T.
Benzylaminoethyureido-Tailed Benzenesulfonamides: Design, Synthesis, Kinetic and X-ray Investigations on Human Carbonic Anhydrases.
Int J Mol Sci, 21:-, 2020

PubMed Abstract: A drug design strategy of carbonic anhydrase inhibitors (CAIs) belonging to sulfonamides incorporating ureidoethylaminobenzyl tails is presented. A variety of substitution patterns on the ring and the tails, located on - or - positions with respect to the sulfonamide warheads were incorporated in the new compounds. Inhibition of human carbonic anhydrases (hCA) isoforms I, II, IX and XII, involving various pathologies, was assessed with the new compounds. Selective inhibitory profile towards hCA II was observed, the most active compounds being low nM inhibitors (s of 2.8-9.2 nM, respectively). Extensive X-ray crystallographic analysis of several sulfonamides in an adduct with hCA I allowed an in-depth understanding of their binding mode and to lay a detailed structure-activity relationship.

PubMed: 32272689
DOI: 10.3390/ijms21072560

Experimental method

X-RAY DIFFRACTION (1.55 Å)