4KP8: Crystal Structure of Catalytic Domain of Human Carbonic Anhydrase Isozyme XII With 3-[(pyrimidin-2-ylsulfanyl)acetyl]benzenesulfonamide

Citation:
Abstract
Two groups of benzenesulfonamide derivatives, bearing pyrimidine moieties, were designed and synthesized as inhibitors of carbonic anhydrases (CA). Their binding affinities to six recombinant human CA isoforms I, II, VI, VII, XII, and XIII were determined by the thermal shift assay (TSA). The binding of several inhibitors was measured by isothermal titration calorimetry (ITC). Direct demonstration of compound inhibition was achieved by determining the inhibition constant by stopped-flow CO2 hydration assay. The most potent compounds demonstrated selectivity towards isoform I and affinities of 0.5nM. The crystal structures of selected compounds in complex with CA II, XII, and XIII were determined to atomic resolution. Compounds described here were compared with previously published pyrimidinebenzenesulfonamides.(1) Systematic structure-activity analysis of 40 compound interactions with six isoforms yields clues for the design of compounds with greater affinities and selectivities towards target CA isoforms.
PDB ID: 4KP8Download
MMDB ID: 114898
PDB Deposition Date: 2013/5/13
Updated in MMDB: 2013/11
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 4KP8: dimeric; determined by author
Molecular Components in 4KP8
Label Count Molecule
Proteins (2 molecules)
2
Carbonic Anhydrase 12
Molecule annotation
Chemicals (7 molecules)
1
2
2
2
3
1
4
1
5
1
* Click molecule labels to explore molecular sequence information.

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