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8co0

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Three dimensional structure of human carbonic anhydrase IX in complex with sulfonamide

Structural highlights

8co0 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CAH9_HUMAN Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.^[1]

Publication Abstract from PubMed

Here, we report for the first time a series of sulfonamide derivatives with scaffolds bearing flexible moieties, namely, rotamers or tropoisomers capable of adapting their geometry in the active center of enzymes thus being effective and selective carbonic anhydrase (CAs, EC 4.2.1.1) enzyme inhibitors. All compounds exhibited effective in vitro inhibition activity toward the main hCA isoforms related to cancer (i.e., hCA II, hCA IX, and hCA XII with K(I) values in the low nanomolar range). Three selected compounds showed a great cytotoxic effect on cancer cell lines ex vivo. X-ray crystallographic experiments assessed the binding modes of compound 35 with active centers of hCA IX and hCA XII.

Atropo/Tropo Flexibility: A Tool for Design and Synthesis of Self-Adaptable Inhibitors of Carbonic Anhydrases and Their Antiproliferative Effect.,Ivanova JN, Nocentini A, Ta Rs K, Leita Ns JN, Dvinskis E, Kazaks A, Domraceva I, Supuran CT, Zalubovskis R J Med Chem. 2023 Apr 27;66(8):5703-5718. doi: 10.1021/acs.jmedchem.3c00007. Epub , 2023 Apr 6. PMID:37022308^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hilvo M, Baranauskiene L, Salzano AM, Scaloni A, Matulis D, Innocenti A, Scozzafava A, Monti SM, Di Fiore A, De Simone G, Lindfors M, Janis J, Valjakka J, Pastorekova S, Pastorek J, Kulomaa MS, Nordlund HR, Supuran CT, Parkkila S. Biochemical characterization of CA IX, one of the most active carbonic anhydrase isozymes. J Biol Chem. 2008 Oct 10;283(41):27799-809. doi: 10.1074/jbc.M800938200. Epub, 2008 Aug 13. PMID:18703501 doi:http://dx.doi.org/10.1074/jbc.M800938200
↑ Ivanova JN, Nocentini A, Ta Rs K, Leita Ns JN, Dvinskis E, Kazaks A, Domračeva I, Supuran CT, Žalubovskis R. Atropo/Tropo Flexibility: A Tool for Design and Synthesis of Self-Adaptable Inhibitors of Carbonic Anhydrases and Their Antiproliferative Effect. J Med Chem. 2023 Apr 27;66(8):5703-5718. PMID:37022308 doi:10.1021/acs.jmedchem.3c00007