5t30
Human MnSOD-azide complexHuman MnSOD-azide complex
Structural highlights
Disease[SODM_HUMAN] Genetic variation in SOD2 is associated with susceptibility to microvascular complications of diabetes type 6 (MVCD6) [MIM:612634]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Function[SODM_HUMAN] Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.[1] Publication Abstract from PubMedSuperoxide dismutases (SODs) are enzymes that play a key role in protecting cells from toxic oxygen metabolites by disproportionation of two molecules of superoxide into molecular oxygen and hydrogen peroxide via cyclic reduction and oxidation at the active site metal. The azide anion is a potent competitive inhibitor that binds directly to the metal and is used as a substrate analog to superoxide in studies of SOD. The crystal structure of human MnSOD-azide complex was solved and shows the putative binding position of superoxide, providing a model for binding to the active site. Azide is bound end-on at the sixth coordinate position of the manganese ion. Tetrameric electrostatic surfaces were calculated incorporating accurate partial charges for the active site in three states, including a state with superoxide coordinated to the metal using the position of azide as a model. These show facilitation of the anionic ligand to the active site pit via a 'valley' of positively-charged surface patches. Surrounding ridges of negative charge help guide the superoxide anion. Within the active site pit, Arg173 and Glu162 further guide and align superoxide for efficient catalysis. Superoxide coordination at the sixth position causes the electrostatic surface of the active site pit to become nearly neutral. A model for electrostatic-mediated diffusion, and efficient binding of superoxide for catalysis is presented. Substrate-analog binding and electrostatic surfaces of human manganese superoxide dismutase.,Azadmanesh J, Trickel SR, Borgstahl GEO J Struct Biol. 2017 Apr 29. pii: S1047-8477(17)30064-3. doi:, 10.1016/j.jsb.2017.04.011. PMID:28461152[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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