Biomaterial Database

Expression, purification, and characterization of a familial amyotrophic lateral sclerosis-associated D90A Cu,Zn-superoxide dismutase mutant. 1998

S M Kim, and W S Eum, and J H Kang

Department of Genetic Engineering, Chongju University, Korea.

Cu,Zn-superoxide dismutase (SOD) is known to be a locus of mutation in familial amyotrophic lateral sclerosis (FALS). We cloned the FALS mutant, D90A, and wild-type of human Cu,Zn-SOD, overexpressed them in E. coli, purified the proteins, and studied their properties. We investigated their enzymic activities for catalyzing the dismutation of superoxide anions and the generation of free radicals with H2O2 as a substrate. Our results showed that both wild-type and mutant enzymes have identical dismutation activities. However, the hydroxyl radical-generating function of the D90A mutant, as measured using a 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate), was enhanced relative to that of the wild-type enzyme. Catalysis of this reaction by D90A was more sensitive to inhibition by the copper chelators, penicillamine and diethyldithiocarbamate, than was catalysis by wild-type Cu,Zn-SOD. Our study suggests that this gain-of-function of FALS mutant may, in part, be responsible for the development of FALS symptoms.

UI	MeSH Term	Description	Entries
D011993	Recombinant Fusion Proteins	Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.	Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D002614	Chelating Agents	Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.	Chelating Agent,Chelator,Complexons,Metal Antagonists,Chelators,Metal Chelating Agents,Agent, Chelating,Agents, Chelating,Agents, Metal Chelating,Antagonists, Metal,Chelating Agents, Metal
D003300	Copper	A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.	Copper-63,Copper 63
D005609	Free Radicals	Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.	Free Radical
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000409	Alanine	A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.	Abufène,Alanine, L-Isomer,L-Alanine,Alanine, L Isomer,L Alanine,L-Isomer Alanine
D000690	Amyotrophic Lateral Sclerosis	A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94)	ALS - Amyotrophic Lateral Sclerosis,Lou Gehrig Disease,Motor Neuron Disease, Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis With Dementia,Amyotrophic Lateral Sclerosis, Guam Form,Amyotrophic Lateral Sclerosis, Parkinsonism-Dementia Complex of Guam,Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia Complex 1,Charcot Disease,Dementia With Amyotrophic Lateral Sclerosis,Gehrig's Disease,Guam Disease,Guam Form of Amyotrophic Lateral Sclerosis,Lou Gehrig's Disease,Lou-Gehrigs Disease,ALS Amyotrophic Lateral Sclerosis,Amyotrophic Lateral Sclerosis Parkinsonism Dementia Complex 1,Amyotrophic Lateral Sclerosis, Parkinsonism Dementia Complex of Guam,Disease, Guam,Disease, Lou-Gehrigs,Gehrig Disease,Gehrigs Disease,Sclerosis, Amyotrophic Lateral
D001224	Aspartic Acid	One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.	(+-)-Aspartic Acid,(R,S)-Aspartic Acid,Ammonium Aspartate,Aspartate,Aspartate Magnesium Hydrochloride,Aspartic Acid, Ammonium Salt,Aspartic Acid, Calcium Salt,Aspartic Acid, Dipotassium Salt,Aspartic Acid, Disodium Salt,Aspartic Acid, Hydrobromide,Aspartic Acid, Hydrochloride,Aspartic Acid, Magnesium (1:1) Salt, Hydrochloride, Trihydrate,Aspartic Acid, Magnesium (2:1) Salt,Aspartic Acid, Magnesium-Potassium (2:1:2) Salt,Aspartic Acid, Monopotassium Salt,Aspartic Acid, Monosodium Salt,Aspartic Acid, Potassium Salt,Aspartic Acid, Sodium Salt,Calcium Aspartate,Dipotassium Aspartate,Disodium Aspartate,L-Aspartate,L-Aspartic Acid,Magnesiocard,Magnesium Aspartate,Mg-5-Longoral,Monopotassium Aspartate,Monosodium Aspartate,Potassium Aspartate,Sodium Aspartate,Aspartate, Ammonium,Aspartate, Calcium,Aspartate, Dipotassium,Aspartate, Disodium,Aspartate, Magnesium,Aspartate, Monopotassium,Aspartate, Monosodium,Aspartate, Potassium,Aspartate, Sodium,L Aspartate,L Aspartic Acid
D013482	Superoxide Dismutase	An oxidoreductase that catalyzes the reaction between SUPEROXIDES and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide.	Hemocuprein,Ag-Zn Superoxide Dismutase,Cobalt Superoxide Dismutase,Cu-Superoxide Dismutase,Erythrocuprein,Fe-Superoxide Dismutase,Fe-Zn Superoxide Dismutase,Iron Superoxide Dismutase,Manganese Superoxide Dismutase,Mn-SOD,Mn-Superoxide Dismutase,Ag Zn Superoxide Dismutase,Cu Superoxide Dismutase,Dismutase, Ag-Zn Superoxide,Dismutase, Cobalt Superoxide,Dismutase, Cu-Superoxide,Dismutase, Fe-Superoxide,Dismutase, Fe-Zn Superoxide,Dismutase, Iron Superoxide,Dismutase, Manganese Superoxide,Dismutase, Mn-Superoxide,Dismutase, Superoxide,Fe Superoxide Dismutase,Fe Zn Superoxide Dismutase,Mn SOD,Mn Superoxide Dismutase,Superoxide Dismutase, Ag-Zn,Superoxide Dismutase, Cobalt,Superoxide Dismutase, Fe-Zn,Superoxide Dismutase, Iron,Superoxide Dismutase, Manganese
D015870	Gene Expression	The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.	Expression, Gene,Expressions, Gene,Gene Expressions