3gz0
Apo-human carbonic anhydrase II revisited: Implications of the loss of a metal in protein structure, stability and solvent network
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 Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman carbonic anhydrase II (HCA II) is a monomeric zinc-containing metalloenzyme that catalyzes the hydration of CO2 to form bicarbonate and a proton. The properties of the zinc have been extensively elucidated in catalysis, but less well studied as a contributor to structure and stability. Apo-HCA II (without zinc) was prepared and compared to holo-HCA II; in crystallographic structural features, in backbone amide H/D exchange, and in thermal stability. The removal of zinc from the active site has no effect on either the topological fold of the enzyme or the ordered water network in the active site. However, the removal of the zinc alters the collective electrostatics of the apo-HCA II that result in the following differences from that of the holoenzyme; 1) the main thermal unfolding transition of the apo-HCA II is lowered by 8 masculineC, 2) the relative increase in thermal mobility of atoms of the apo-HCA II was not observed in the vicinity of the active site but manifested on the surface of the enzyme, and 3) the side chain of His 64, the proton shuttle residue that sits on the rim of the active site, is oriented outwards and is associated with additional ordered "external" waters, as opposed to a near equal inward and outward orientation in the holo-HCA II. Apo-Human Carbonic Anhydrase II Revisited: Implications of the Loss of a Metal in Protein Structure, Stability and Solvent Network.,Avvaru BS, Busby SA, Chalmers MJ, Griffin PR, Venkatakrishnan B, Agbandje-McKenna M, Silverman DN, McKenna R Biochemistry. 2009 Jul 7. PMID:19583303[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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