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1jcz
From Proteopedia
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CRYSTAL STRUCTURE OF THE EXTRACELLULAR DOMAIN OF HUMAN CARBONIC ANHYDRASE XII
Overview
Overexpression of the zinc enzyme carbonic anhydrase (CA; EC ) XII is, observed in certain human cancers. This bitopic membrane protein contains, an N-terminal extracellular catalytic domain, a membrane-spanning, alpha-helix, and a small intracellular C-terminal domain. We have, determined the three-dimensional structure of the extracellular catalytic, domain of human CA XII by x-ray crystallographic methods at 1.55-A, resolution. The structure reveals a prototypical CA fold; however, two CA, XII domains associate to form an isologous dimer, an observation that is, confirmed by studies of the enzyme in solution. The identification of, signature GXXXG and GXXXS motifs in the transmembrane sequence that, facilitate helix-helix association is additionally consistent with dimeric, architecture. The dimer interface is situated so that the active site, clefts of each monomer are clearly exposed on one face of the dimer, and, the C termini are located together on the opposite face of the dimer to, facilitate membrane interaction. The amino acid composition of the, active-site cleft closely resembles that of the other CA isozymes in the, immediate vicinity of the catalytic zinc ion, but differs in the region of, the nearby alpha-helical "130's segment." The structure of the CA, XII-acetazolamide complex is also reported at 1.50-A resolution, and, prospects for the design of CA XII-specific inhibitors of possible, chemotherapeutic value are discussed.
About this Structure
1JCZ is a Single protein structure of sequence from Homo sapiens with ZN and ACY as ligands. Active as Carbonate dehydratase, with EC number 4.2.1.1 Full crystallographic information is available from OCA.
Reference
Crystal structure of the dimeric extracellular domain of human carbonic anhydrase XII, a bitopic membrane protein overexpressed in certain cancer tumor cells., Whittington DA, Waheed A, Ulmasov B, Shah GN, Grubb JH, Sly WS, Christianson DW, Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9545-50. Epub 2001 Aug 7. PMID:11493685
Page seeded by OCA on Mon Nov 12 17:39:36 2007
