2hkk
From Proteopedia
Carbonic anhydrase activators: Solution and X-ray crystallography for the interaction of andrenaline with various carbonic anhydrase isoforms
Structural highlights
DiseaseCAH2_HUMAN Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:259730; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.[1] [2] [3] [4] [5] FunctionCAH2_HUMAN Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.[6] [7] Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe activation of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) with L-adrenaline and histamine has been investigated by kinetic and X-ray crystallographic studies. L-Adrenaline behaves as a potent activator of isozyme CA I (activation constant of 90 nM), being a much weaker activator of isozyme CA II (activation constant of 96 microM). Isoforms CA IV, VA, VII, and XIV were activated by L-adrenaline with K(A)s in the range of 36-63 microM. The X-ray crystal structure of the CA II-L-adrenaline adduct revealed that the activator plugs the entrance of the active site cavity, obstructing it almost completely. Carbonic anhydrase activators: L-Adrenaline plugs the active site entrance of isozyme II, activating better isoforms I, IV, VA, VII, and XIV.,Temperini C, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT Bioorg Med Chem Lett. 2007 Feb 1;17(3):628-35. Epub 2006 Nov 15. PMID:17127057[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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