Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nuclear gene atp1 encoding the mitochondrial ATP synthase alpha subunit of the fission yeast Schizosaccharomyces pombe was sequenced. It contains a 1,608-base pair-long open reading frame interrupted by two introns of 175 and 269 base pairs, located near the 5'-end of the gene. The initiation site of transcription AAAC was located 60 nucleotides upstream of the translation initiation codon. The deduced polypeptide sequence contains a 27-amino acid residue presequence, presumably involved in mitochondrial targeting, preceding a mature protein of 509 amino acid residues. The atp1 alleles from mutant A2313 (Bouty, M., and Goffeau, A. (1982) Eur. J. Biochem. 125, 471-477) and its related phenotypic revertant R351 (Falson, P., Di Pietro, A., Darbouret, D., Jault, J. M., Gautheron, D. C., Boutry, M., and Goffeau, A. (1987) Biochem. Biophys. Res. Commun. 148, 1182-1188) were also cloned and sequenced. A single nonsense mutation CAA-TAA (Gln173-stop) in mutant A2313 became a missense mutation TAA-TTA (stop-Leucine) in revertant R351. Glutamine 173 is located in the first putative element of the nucleotide binding site. Its substitution by a leucine residue appears responsible for the lower enzyme affinity toward ADP and for the loss of cooperativity of F1-ATPase activity.
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PMID:Alpha subunit of mitochondrial F1-ATPase from the fission yeast. Deduced sequence of the wild type and identification of a mutation that alters apparent negative cooperativity. 182 97

The beta-amyloid (A beta) peptide is present both in serum and in platelets, however it is unclear whether A beta plays a role in platelet function. We have now investigated the effects of soluble A beta on platelet function and have found that low levels (0.1-1 nM) of soluble A beta augment ADP-dependent platelet aggregation and translocation of focal adhesion kinase to the platelet cytoskeleton. Addition of A beta to gel-filtered platelets along with concentrations of adenosine diphosphate (ADP) producing submaximal aggregation responses increased the aggregation response by over 2-fold depending on the ADP:A beta ratios. The structure activity requirements for A beta activity showed intriguing constraints. Only full length A beta has significant activity. Truncated A beta peptides, such as A beta(1-16) or A beta(25-35), or reverse A beta(40-1) all show little or no activity. We also examined the activity of mutant A beta peptides, corresponding with the APP(692A-G) and APP(693E-Q) (at A beta21 and A beta22, respectively) which are found in familial Alzheimer's disease and hereditary cerebral hemorrhagic amyloidosis, Dutch type (HCHWA-D), and found that these peptides showed little or no activity. These results suggest that A beta interacts with platelets in a highly specific manner and may play a role in regulating platelet function.
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PMID:Beta-amyloid augments platelet aggregation: reduced activity of familial angiopathy-associated mutants. 985 75

A specific feature of anthraquinone dyes (AD) is to mimic the adenine nucleotides ATP, ADP, NAD and NADH, enabling them to act as ligands in interaction with nucleotide-binding sites of several enzymes and receptors. In the present study, the interactions and/or inhibitory effects of eight AD, including Cibacron Blue 3G-A (Reactive Blue 2), Procion Blue MX-R (Reactive Blue 4) and Remazol Brilliant Blue R (Reactive Blue 19) on the activity of (Na(+)/K(+))-ATPase were investigated. The AD used in this paper could be divided into two groups: i) AD1-AD4 that do not contain the triazine moiety; ii) AD5-AD8 that contain the triazine moiety. Interaction affinity between the respective dye and (Na+/K+)-ATPase was characterized by means of enzyme kinetics. All AD, excluding AD1 and AD2 (which were practically ineffective) exerted effective competitive inhibition to the (Na(+)/K(+))-ATPase activity. Present study is devoted to elucidation of relationship between the inhibitory efficacy of AD against (Na(+)/K(+))-ATPase activity, their acid-basic properties and their three dimensional structure. From the results obtained, the following conclusions could be driven: 1. Similarities in the mutual position of positively and negatively charged parts of ATP and AD are responsible for their interaction with ATP-binding site of (Na(+)/K(+))-ATPase. This may be documented by fact that mutual position of 1-aminogroup of anthraquinone and -SO3(-) group of benzenesulphonate part of respective AD plays crucial role for inhibition of this enzyme. Distances of these two groups on all effective AD were found to be similar as the distance of the 6-aminogroup of adenine and the second phosphate group on ATP molecule. This similarity could be responsible for biomimetic recognition of AD in ATP-binding loci of (Na(+)/K(+))-ATPase. 2. The affinity of AD to ATP binding site of (Na(+)/K(+))-ATPase increases with increasing values of molar refractivity, i. e., with increasing molecular volume and polarizability.
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PMID:Inhibition of (Na(+)/K(+))-ATPase by Cibacron Blue 3G-A and its analogues. 1735 35