1a42: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 6: | Line 6: | ||
==Overview== | ==Overview== | ||
Carbonic anhydrase IV (CAIV) is a membrane-associated enzyme anchored to, plasma membrane surfaces by a phosphatidylinositol glycan linkage. We have, determined the 2.8-angstroms resolution crystal structure of a truncated, soluble form of recombinant murine CAIV. We have also determined the, structure of its complex with a drug used for glaucoma therapy, the, sulfonamide inhibitor brinzolamide (Azopt). The overall structure of, murine CAIV is generally similar to that of human CAIV; however, some, local structural differences are found in the active site resulting from, amino acid sequence differences in the "130's segment" and the residue-63, loop (these may affect the nearby catalytic proton shuttle, His-64)., Similar to human CAIV, the C-terminus of murine CAIV is surrounded by a, substantial electropositive surface potential that may stabilize the, interaction with the phospholipid membrane. Binding interactions observed, for brinzolamide rationalize the generally weaker affinity of inhibitors, used in glaucoma therapy toward CAIV compared with CAII. | Carbonic anhydrase IV (CAIV) is a membrane-associated enzyme anchored to, plasma membrane surfaces by a phosphatidylinositol glycan linkage. We have, determined the 2.8-angstroms resolution crystal structure of a truncated, soluble form of recombinant murine CAIV. We have also determined the, structure of its complex with a drug used for glaucoma therapy, the, sulfonamide inhibitor brinzolamide (Azopt). The overall structure of, murine CAIV is generally similar to that of human CAIV; however, some, local structural differences are found in the active site resulting from, amino acid sequence differences in the "130's segment" and the residue-63, loop (these may affect the nearby catalytic proton shuttle, His-64)., Similar to human CAIV, the C-terminus of murine CAIV is surrounded by a, substantial electropositive surface potential that may stabilize the, interaction with the phospholipid membrane. Binding interactions observed, for brinzolamide rationalize the generally weaker affinity of inhibitors, used in glaucoma therapy toward CAIV compared with CAII. | ||
==Disease== | |||
Known disease associated with this structure: Osteopetrosis, autosomal recessive 3, with renal tubular acidosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=611492 611492]] | |||
==About this Structure== | ==About this Structure== | ||
| Line 24: | Line 27: | ||
[[Category: zinc]] | [[Category: zinc]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 15:55:20 2007'' | ||
