8co3

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

Structural highlights

8co3 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 1.68Å
Ligands:V8O, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CAH12_HUMAN Defects in CA12 are the cause of hyperchlorhidrosis isolated (HCHLH) [MIM:143860. HCHLH is a disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat.[1]

Function

CAH12_HUMAN Reversible hydration of carbon dioxide.

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.

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Citations
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"Cicada Out of the Shell" Deep Penetration and Blockage of the HSP90 Pathway by ROS-Responsive Supramolecular Gels to Augment Trimodal Synergistic Therapy.
Li et al. (2024)
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References

  1. ↑ Feldshtein M, Elkrinawi S, Yerushalmi B, Marcus B, Vullo D, Romi H, Ofir R, Landau D, Sivan S, Supuran CT, Birk OS. Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII. Am J Hum Genet. 2010 Nov 12;87(5):713-20. doi: 10.1016/j.ajhg.2010.10.008. Epub, 2010 Oct 28. PMID:21035102 doi:10.1016/j.ajhg.2010.10.008
  2. ↑ 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

Contents


PDB ID 8co3

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OCA

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