PMID- 10400992
OWN - NLM
STAT- MEDLINE
DCOM- 19990914
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 8
DP  - 1999 Aug
TI  - Variation in the biochemical/biophysical properties of mutant superoxide
      dismutase 1 enzymes and the rate of disease progression in familial amyotrophic
      lateral sclerosis kindreds.
PG  - 1451-60
AB  - Mutations in superoxide dismutase 1 (SOD1) polypeptides cause a form of familial 
      amyotrophic lateral sclerosis (FALS). In different kindreds, harboring different 
      mutations, the duration of illness tends to be similar for a given mutation. For 
      example, patients inheriting a substitution of valine for alanine at position
      four (A4V) average a 1.5 year life expectancy after the onset of symptoms,
      whereas patients harboring a substitution of arginine for histidine at position
      46 (H46R) average an 18 year life expectancy after disease onset. Here, we
      examine a number of biochemical and biophysical properties of nine different FALS
      variants of SOD1 polypeptides, including enzymatic activity (which relates
      indirectly to the affinity of the enzyme for copper), polypeptide half-life,
      resistance to proteolytic degradation and solubility, in an effort to determine
      whether a specific property of these enzymes correlates with clinical
      progression. We find that although all the mutants tested appear to be soluble,
      the different mutants show a remarkable degree of variation with respect to
      activity, polypeptide half-life and resistance to proteolysis. However, these
      variables do not stratify in a manner that correlates with clinical progression. 
      We conclude that the basis for the different life expectancies of patients in
      different kindreds of sod1-linked FALS may result from an as yet unidentified
      property of these mutant enzymes.
FAU - Ratovitski, T
AU  - Ratovitski T
AD  - Department of Pathology, Johns Hopkins School of Medicine, 558 Ross Building, 720
      Rutland Avenue, Baltimore, MD 21205, USA,
FAU - Corson, L B
AU  - Corson LB
FAU - Strain, J
AU  - Strain J
FAU - Wong, P
AU  - Wong P
FAU - Cleveland, D W
AU  - Cleveland DW
FAU - Culotta, V C
AU  - Culotta VC
FAU - Borchelt, D R
AU  - Borchelt DR
LA  - eng
GR  - 1 R01 NS 37145/NS/NINDS NIH HHS/United States
GR  - 1 R01 NS 37225/NS/NINDS NIH HHS/United States
GR  - GM 50016/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (SOD1 protein, human)
RN  - 4QD397987E (Histidine)
RN  - 789U1901C5 (Copper)
RN  - EC 1.15.1.1 (Sod1 protein, mouse)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
RN  - EC 3.4.21.64 (Endopeptidase K)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Amino Acid Substitution
MH  - Amyotrophic Lateral Sclerosis/enzymology/*genetics/pathology
MH  - Animals
MH  - COS Cells
MH  - Centrifugation
MH  - Copper/metabolism
MH  - Disease Progression
MH  - Endopeptidase K/metabolism
MH  - Family Health
MH  - Genetic Variation
MH  - Glycine/genetics
MH  - Histidine/genetics
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Mutation
MH  - Protein Binding
MH  - Solubility
MH  - Superoxide Dismutase/chemistry/*genetics/metabolism
MH  - Superoxide Dismutase-1
MH  - Time Factors
MH  - Tumor Cells, Cultured
EDAT- 1999/07/13 00:00
MHDA- 1999/07/13 00:01
CRDT- 1999/07/13 00:00
PHST- 1999/07/13 00:00 [pubmed]
PHST- 1999/07/13 00:01 [medline]
PHST- 1999/07/13 00:00 [entrez]
AID - ddc158 [pii]
AID - 10.1093/hmg/8.8.1451 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Aug;8(8):1451-60. doi: 10.1093/hmg/8.8.1451.