ABCD1 p.Glu487Lys
| Predicted by SNAP2: | A: N (57%), C: N (61%), D: N (97%), F: D (59%), G: D (59%), H: N (66%), I: N (57%), K: D (59%), L: N (53%), M: N (53%), N: N (66%), P: D (59%), Q: N (72%), R: D (53%), S: N (57%), T: N (66%), V: N (61%), W: N (57%), Y: N (53%), |
| Predicted by PROVEAN: | A: D, C: D, D: N, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: N, P: D, Q: N, R: D, S: N, T: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Characterization of E. coli tetrameric aldehyde de... Protein Sci. 2006 Jun;15(6):1387-96. Rodriguez-Zavala JS, Allali-Hassani A, Weiner H
Characterization of E. coli tetrameric aldehyde dehydrogenases with atypical properties compared to other aldehyde dehydrogenases.
Protein Sci. 2006 Jun;15(6):1387-96., [PMID:16731973]
Abstract [show]
Aldehyde dehydrogenases are general detoxifying enzymes, but there are also isoenzymes that are involved in specific metabolic pathways in different organisms. Two of these enzymes are Escherichia coli lactaldehyde (ALD) and phenylacetaldehyde dehydrogenases (PAD), which participate in the metabolism of fucose and phenylalanine, respectively. These isozymes share some properties with the better characterized mammalian enzymes but have kinetic properties that are unique. It was possible to thread the sequences into the known ones for the mammalian isozymes to better understand some structural differences. Both isozymes were homotetramers, but PAD used both NAD+ and NADP+ but with a clear preference for NAD, while ALD used only NAD+. The rate-limiting step for PAD was hydride transfer as indicated by the primary isotopic effect and the absence of a pre-steady-state burst, something not previously found for tetrameric enzymes from other organisms where the rate-limiting step is related to both deacylation and coenzyme dissociation. In contrast, ALD had a pre-steady-state burst indicating that the rate-limiting step was located after the NADH formation, but the rate-limiting step was a combination of deacylation and coenzyme dissociation. Both enzymes possessed esterase activity that was stimulated by NADH; NAD+ stimulated the esterase activity of PAD but not of ALD. Finding enzymes that structurally are similar to the well-characterized mammalian enzymes but have a different rate-limiting step might serve as models to allow us to determine what regulates the rate-limiting step.
Comments [show]
None has been submitted yet.
No. Sentence Comment
160 The structure of the E487K enzyme revealed that the coenzyme-binding domain is destroyed, showing why NAD+ binds with such difficulty to the Asian variant (Larson et al. 2005).
X
ABCD1 p.Glu487Lys 16731973:160:21
status: NEW[hide] Polymorphisms of alcohol-metabolizing enzymes and ... Drug Alcohol Depend. 2006 Sep 15;84(2):195-200. Epub 2006 Apr 5. Lorenzo A, Auguet T, Vidal F, Broch M, Olona M, Gutierrez C, Lopez-Dupla M, Sirvent JJ, Quer JC, Santos M, Richart C
Polymorphisms of alcohol-metabolizing enzymes and the risk for alcoholism and alcoholic liver disease in Caucasian Spanish women.
Drug Alcohol Depend. 2006 Sep 15;84(2):195-200. Epub 2006 Apr 5., [PMID:16600530]
Abstract [show]
BACKGROUND: The relationship of polymorphisms of the genes that encode for alcohol-metabolizing enzymes and individual vulnerability to alcoholism and alcoholic liver disease (ALD) in women is unclear. We determined the genotypes of ADH1B, ADH1C, CYP2E1 (Dra-I and Pst-I) and ALDH2 in a group of Caucasian Spanish women. METHODS: We performed a cross-sectional case-control study. The study group was made of 220 women. Of these, 85 were alcoholic (27 without liver disease and 58 with alcoholic liver disease) and 135 were non-alcoholic (42 healthy controls and 93 with liver disease unrelated to alcohol). Genotyping of alcohol-metabolizing enzymes was performed using PCR-RFLP methods. RESULTS: The distribution of the allelic variants (alleles 1 and 2) in the whole subjects analyzed was: ADH1B 91.6% and 8.4%; ADH1C 58.4% and 41.6%; CYP2E1 Dra-I 15% and 85%; CYP2E1 Pst-I 96.8% and 3.2%; and ALDH2 100% and 0%, respectively. Carriage of genotypes containing the ADH1B*2 mutant allele significantly protected against alcoholism [odds-ratio (OR)=0.00; 95% confidence interval (95% CI): 0.00-0.94; p=0.02] but was associated with an increased risk for alcoholic liver disease among alcohol-dependent women [OR=0.43; 95% CI: 0.18-0.41; p=0.004]. Analysis of the remaining loci showed no significant associations. CONCLUSIONS: In Caucasian Spanish women the ADH1B*2 allele modulates the risk for alcohol dependence and for alcoholic liver disease. Given the small number of alcoholic women analyzed here, these data need further validation in larger cohorts.
Comments [show]
None has been submitted yet.
No. Sentence Comment
92 The ALDH2 SNP studied is a G to A transition in exon 12 which translates lysine instead of glutamic acid at the residue 487 (Glu487Lys).
X
ABCD1 p.Glu487Lys 16600530:92:125
status: NEW