5CJF

The crystal structure of the human carbonic anhydrase XIV in complex with a 1,1'-biphenyl-4-sulfonamide inhibitor.

Summary for 5CJF

• Entry DOI: 10.2210/pdb5cjf/pdb
• Related: 4LU3
• Descriptor: Carbonic anhydrase 14, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (7 entities in total)
• Functional Keywords: 1, 1'-biphenyl-4-sulfonamide, lyase, glycoprotein, zinc-binding, complex, inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 32927.63

Authors

Alterio, V.,De Simone, G. (deposition date: 2015-07-14, release date: 2015-11-04, Last modification date: 2024-11-20)

Primary citation

La Regina, G.,Coluccia, A.,Famiglini, V.,Pelliccia, S.,Monti, L.,Vullo, D.,Nuti, E.,Alterio, V.,De Simone, G.,Monti, S.M.,Pan, P.,Parkkila, S.,Supuran, C.T.,Rossello, A.,Silvestri, R.
Discovery of 1,1'-Biphenyl-4-sulfonamides as a New Class of Potent and Selective Carbonic Anhydrase XIV Inhibitors.
J.Med.Chem., 58:8564-8572, 2015

PubMed Abstract: New 1,1'-biphenylsulfonamides were synthesized and evaluated as inhibitors of the ubiquitous human carbonic anhydrase isoforms I, II, IX, XII, and XIV using acetazolamide (AAZ) as reference compound. The sulfonamides 1-21 inhibited all the isoforms, with Ki values in the nanomolar range of concentration, and were superior to AAZ against all of them. X-ray crystallography and molecular modeling studies on the adducts that compound 20, the most potent hCA XIV inhibitor of the series (Ki = 0.26 nM), formed with the five hCAs, provided insight into the molecular determinants responsible for the high affinity of this molecule toward the target enzymes. The results pave the way to the development of 1.1'-biphenylsulfonamides as a new class of highy potent hCA XIV inhibitors.

PubMed: 26497049
DOI: 10.1021/acs.jmedchem.5b01144

Experimental method

X-RAY DIFFRACTION (1.83 Å)