4ZWZ: Engineered Carbonic Anhydrase Ix Mimic In Complex With A Glucosyl Sulfamate Inhibitor

Citation:
Abstract
Inhibition of human carbonic anhydrase IX (hCA IX) has shown to be therapeutically advantageous for treating many types of highly aggressive cancers. However, designing selective inhibitors for hCA IX has been difficult due to its high structural homology and sequence similarity with off-target hCAs. Recently, the use of glucosyl sulfamate inhibitors has shown promise as selective inhibitors for hCA IX. In this study, we present five X-ray crystal structures, determined to a resolution of 1.7 A or better, of both hCA II (a ubiquitous CA) and an engineered hCA IX-mimic in complex with selected glucosyl sulfamates and structurally rationalize mechanisms for hCA IX selectivity. Results from this study have allowed us, for the first time, to empirically "map" key interactions of the hCA IX active site in order to establish parameters needed to design novel hCA IX selective inhibitors.
PDB ID: 4ZWZDownload
MMDB ID: 131499
PDB Deposition Date: 2015/5/19
Updated in MMDB: 2015/09
Experimental Method:
x-ray diffraction
Resolution: 1.62  Å
Similar Structures:
Biological Unit for 4ZWZ: monomeric; determined by author and by software (PISA)
Molecular Components in 4ZWZ
Label Count Molecule
Protein (1 molecule)
1
Carbonic Anhydrase 2(Gene symbol: CA2)
Molecule annotation
Chemicals (4 molecules)
1
1
2
1
3
2
* Click molecule labels to explore molecular sequence information.

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