Disease relevance of valine

• Here we describe a family with X-linked dyserythropoietic anaemia and thrombocytopenia due to a substitution of methionine for valine at amino acid 205 of GATA-1 [1].
• A more commonly distributed transition causing a valine to isoleucine switch in transmembrane domain I of CCR2B (64I) with unknown functional consequences was recently shown to delay disease progression but not reduce infection risk [2].
• Enlarging the amino acid set of Escherichia coli by infiltration of the valine coding pathway [3].
• A polymorphism at codon 655 (GTC/valine to ATC /isoleucine [Val(655)Ile]) in the transmembrane domain-coding region of this gene has been identified and may be associated with the risk of breast cancer [4].
• Maple syrup urine disease (MSUD) or branched-chain alpha-ketoaciduria is an autosomally inherited disorder in the catabolism of branched-chain amino acids leucine, isoleucine, and valine [5].

Psychiatry related information on valine

• Examination of the prion protein genes of all these cases and of a single case of gonadotropin-related CJD showed that 4 had the uncommon valine 129 homozygous genotype indicating genetic susceptibility to prion infection [6].
• Finally, a rare phenotype characterized by progressive dementia was linked to PrP(Sc) type 1 and valine homozygosity [7].
• Ten affected individuals are described from a kindred with autosomal dominant familial Alzheimer's disease in which a mutation in the amyloid precursor protein gene results in a valine to glycine substitution at amyloid precursor protein 717 which co-segregates with the disease [8].
• The val66met single-nucleotide polymorphism (SNP) showed significant (P = 0.005) association for valine (allele G) with schizophrenia but not bipolar disorder [9].
• In the nuclear families, significant transmission disequilibrium for the valine allele was observed between the alleles of the Val158Met COMT polymorphism and panic disorder (p<0.01) [10].

High impact information on valine

• Here, we report about a surprising interaction between TYMV-RNA-programmed ribosomes and 3'-valylated TLS that yields polyprotein with the valine N terminally incorporated by a translation mechanism resistant to regular initiation inhibitors [11].
• The 3'-untranslated region harbors a tRNA-like structure (TLS) to which a valine moiety can be added and it is indispensable for virus viability [11].
• This highly conserved valine is necessary for interaction of the amino-terminal zinc finger of GATA-1 with its essential cofactor, FOG-1 (for friend of GATA-1; refs 9-12) [1].
• Threonyl-tRNA synthetase, a class II synthetase, uses a unique zinc ion to discriminate against the isosteric valine at the activation step [12].
• We also found that the mouse I7 receptor, unlike the rat I7 receptor, prefers heptanal instead of octanal, as a result of a single valine-to-isoleucine substitution [13].

Chemical compound and disease context of valine

• We describe a highly disabling congenital myasthenic syndrome (CMS) associated with rapidly decaying, low-amplitude synaptic currents, and trace its cause to a valine to leucine mutation in the signature cystine loop (cys-loop) of the AChR alpha subunit [14].
• Two common polymorphisms of the human enzyme have been identified: 677C>T, which leads to the substitution of Ala-222 by valine, and 1298A>C, which leads to the replacement of Glu-429 by alanine; the former polymorphism is the most frequent genetic cause of mild hyperhomocysteinemia, a risk factor for cardiovascular disease [15].
• Pelizaeus-Merzbacher disease: a valine to phenylalanine point mutation in a putative extracellular loop of myelin proteolipid [16].
• All patients with adult sporadic mastocytosis had somatic c-KIT mutations in codon 816 causing substitution of valine for aspartate and spontaneous activation of mast cell growth factor receptor (P = 0.0001) [17].
• In more than 40 chemostat experiments, we were unable to detect any significant differences in mutation rate to bacteriophage T5 resistance or in mutation frequency to valine resistance or tryptophan prototrophy attributable to 40K [18].

Biological context of valine

• A single point mutation changes a valine in the transmembrane domain of the predicted protein product insert to a glutamic acid [19].
• Mutant Ip3 has a single base pair change at the N terminus of 19 kd polypeptide, resulting in the substitution of valine for alanine [20].
• Our studies also suggest that methionine/valine heterozygotes at PRNP codon 129 have a later age of onset of the disease than codon 129 valine/valine homozygotes [21].
• A gene for phenylalanine tRNA is located immediately adjacent to the 5' end of the 12S rRNA gene, a valine tRNA gene occupies the entire region between the 12S and 16S rRNA genes and a leucine tRNA gene is located immediately adjacent to the 3' end of the 16S gene [22].
• The mk allele carries a missense mutation that causes substitution of valine by alanine at amino acid 173 of the p45 NF-E2 protein [23].

Anatomical context of valine

• D-valine as a selective agent for normal human and rodent epithelial cells in culture [24].
• Here we investigate the role of Rac1 in cell transformation and show that Rat1 fibroblasts expressing activated Val-12 Rac1 (Rac1 with valine at residue 12) display all the hallmarks of malignant transformation [25].
• Double-labeling methods established that the increased secretion of the labeled proteins was limited to the potentiated region of a slice; incorporation of labeled valine was increased in the hippocampus if potentiation was through the Schaffer collaterals and in the dentate if potentiation was through the perforant path [26].
• The SVL9 peptide binds Db MHC despite the absence of the consensus binding motif, and a conservative methyl group substitution (Valine 4 <--> Isoleucine) explains why reciprocal T cell responses are elicited in H13a and H13b congenic strains [27].
• One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine) [28].

Associations of valine with other chemical compounds

• DNA sequence analysis revealed two point mutations in highly conserved regions of the gene: an isoleucine to valine change in the PSTAIR region, and a proline to serine change at the C-terminal region of the protein p34 [29].
• Five deviations from the normal genetic sequence of CYP21B were found, but only one appeared likely to affect the functional integrity of the protein: codon 281, GTG, encoding valine, was changed to TTG, leucine [30].
• This mutation converts the initiator ATG (methionine) codon to GTG (valine), blocking initiation of translation at the normal site [31].
• Twenty healthy newborns (two to three days of age) were randomly assigned to receive a feeding consisting either of tryptophan in 10 per cent glucose or valine in 5 per cent glucose (valine competes with tryptophan for entry into the brain) [32].
• The oncogene is activated by a single point mutation (guanine to thymine) resulting in the change glycine to valine at position 12 of p21 (refs 3, 4) [33].

Gene context of valine

• Substitution of Thr 200 by valine as well as knock-out of Jnk2 prevent inactivation and translocation of TIF-IA, leading to stress-resistance of Pol I transcription [34].
• No evidence was found of associations between GSTT1 deficiency or the CYP1A1 valine variant and lung cancer risk due to ETS exposure [35].
• One mutation (G289V) occurred in exon 15 and converted a glycine in a collagenous domain of COL4A5 to a valine [36].
• Mutation of Thr155 to valine is sufficient to stabilize p53 against E6-dependent degradation in reticulocyte lysates and to reduce binding to Mdm2 [37].
• A common human prion-protein-gene (PRNP) polymorphism (encoding either methionine or valine at codon 129) is a strong susceptibility factor for sporadic and acquired prion disease [38].

Analytical, diagnostic and therapeutic context of valine

• Site-directed mutagenesis has been used to construct an active, oxidation-resistant derivative containing a single methionine to valine substitution at the active centre [39].
• Reverse-phase HPLC was also used to isolate the variant tryptic peptide of beta-T13 that has alanine replacing valine at residue 126 [40].
• Sequence analysis of the GLUT-4 gene revealed that one patient was heterozygous for a mutation in which isoleucine (ATC) was substituted for valine (GTC) at position 383 [41].
• Plasma valine and 13C-valine concentrations were measured in 2 healthy volunteers and 2 uraemic patients during and after a 3-hour intravenous infusion of the 13-c-labelled alpha-keto-acid analogue of valine [42].
• Moreover, the pyridinium moieties bound to the chiral L-valine residues in the bridging components of the hosts underwent conformational changes upon inclusion of the guest, as confirmed by circular dichroism spectroscopy and molecular mechanics and dynamics calculations [43].

References