1pm9 | pdb_00001pm9
CRYSTAL STRUCTURE OF HUMAN MNSOD H30N, Y166F MUTANT
Structural highlights
DiseaseSODM_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. FunctionSODM_HUMAN Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.[1] 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 PubMedThe side chains of His30 and Tyr166 from adjacent subunits in the homotetramer human manganese superoxide dismutase (Mn-SOD) form a hydrogen bond across the dimer interface and participate in a hydrogen-bonded network that extends to the active site. Compared with wild-type Mn-SOD, the site-specific mutants H30N, Y166F, and the corresponding double mutant showed 10-fold decreases in steady-state constants for catalysis measured by pulse radiolysis. The observation of no additional effect upon the second mutation is an example of cooperatively interacting residues. A similar effect was observed in the thermal stability of these enzymes; the double mutant did not reduce the major unfolding transition to an extent greater than either single mutant. The crystal structures of these site-specific mutants each have unique conformational changes, but each has lost the hydrogen bond across the dimer interface, which results in a decrease in catalysis. These same mutations caused an enhancement of the dissociation of the product-inhibited complex. That is, His30 and Tyr166 in wild-type Mn-SOD act to prolong the lifetime of the inhibited complex. This would have a selective advantage in blocking a cellular overproduction of toxic H2O2. Amino acid substitution at the dimeric interface of human manganese superoxide dismutase.,Hearn AS, Fan L, Lepock JR, Luba JP, Greenleaf WB, Cabelli DE, Tainer JA, Nick HS, Silverman DN J Biol Chem. 2004 Feb 13;279(7):5861-6. Epub 2003 Nov 24. PMID:14638684[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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