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| AMYOTROPHIC-LATERAL-SCLEROSIS AND STRUCTURAL DEFECTS IN CU,ZN SUPEROXIDE-DISMUTASE |
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| Author(s): DENG HX, HENTATI A, TAINER JA, IQBAL Z, CAYABYAB A, HUNG WY, GETZOFF ED, HU P, HERZFELDT B, ROOS RP, WARNER C, DENG G, SORIANO E, SMYTH C, PARGE HE, AHMED A, ROSES AD, HALLEWELL RA, PERICAKVANCE MA, SIDDIQUE T |
| Source: SCIENCE Volume: 261 Issue: 5124 Pages: 1047-1051 Published: AUG 20 1993 |
| Times Cited: 999 References: 51 |
| Abstract: Single-site mutants in the Cu,Zn superoxide dismutase (SOD) gene (SOD1) occur in patients with the fatal neurodegenerative disorder familial amyotrophic lateral sclerosis (FALS). Complete screening of the SOD1 coding region revealed that the mutation Ala4 to Val in exon 1 was the most frequent one; mutations were identified in exons 2, 4, and 5 but not in the active site region formed by exon 3. The 2.4 angstrom crystal structure of human SOD, along with two other SOD structures, established that all 12 observed FALS mutant sites alter conserved interactions critical to the beta-barrel fold and dimer contact, rather than catalysis. Red cells from heterozygotes had less than 50 percent normal SOD activity, consistent with a structurally defective SOD dimer. Thus, defective SOD is linked to motor neuron death and carries implications for understanding and possible treatment of FALS. |
| Document Type: Article |
| Language: English |
Addresses:
1. NORTHWESTERN UNIV, SCH MED, DEPT NEUROL, 300 E SUPER ST, CHICAGO, IL 60611 USA
2. SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA
3. NORTHWESTERN UNIV, INST NEUROSCI, CHICAGO, IL 60611 USA
4. UNIV CHICAGO, DEPT NEUROL, CHICAGO, IL 60637 USA
5. DENT NEUROL INST, DEPT NEUROL, BUFFALO, NY 14209 USA
6. DUKE UNIV, MED CTR, DEPT MED NEUROL, DURHAM, NC 27710 USA
7. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED, DEPT BIOCHEM, LONDON SW7 2AZ, ENGLAND
8. NORTHWESTERN UNIV, SCH MED, DEPT CELL MOLEC & STRUCT BIOL, CHICAGO, IL 60611 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: LT747 |
| ISSN: 0036-8075 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |