Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cysteine residue 69 of the Escherichia coli Ada transcription factor, which accepts a methyl group from methylphosphotriester in methylated DNA, was substituted by each of 19 other amino acids. Only the mutant Ada (C69H), carrying a histidine substitution of Cys69, exhibited a limited degree of transactivating potential for the ada promoter in E. coli cells although the mutant protein was completely devoid of methylphosphotriester-DNA methyltransferase activity. Using a multicopy plasmid system for the expression of Ada protein, we have shown that Ada C69H has a transactivating capacity equivalent to that of wild-type Ada protein in the absence of an alkylating agent. This indicates that the zinc-binding capacity of histidine at residue 69 is likely to be sufficient for Ada to recognize and bind to the ada promoter. Furthermore, transactivation of the ada promoter by Ada C69H was enhanced up to 6-fold by treatment with methylating agents. An additional substitution was made with alanine in Ada C69H, replacing Cys321, the site for acceptance of a methyl group from O6-methylguanine and O4-methylthymine residues in DNA, with alanine. This renders the protein completely inactive as a methyltransferase but this derivative is constitutively active as a transactivator for the ada promoter. Therefore, acquisition of a methyl group at Cys321 apparently enhances the transactivating capacity of Ada protein on the ada promoter. We propose that the transcription-regulating function of Ada protein is under dual control by methylation of cysteine residues at positions 69 and 321; the former enhances DNA binding, while the latter enhances the transactivating capacity of the protein.
Mol Gen Genet 1996 Mar 20
PMID:Requirement for two conserved cysteine residues in the Ada protein of Escherichia coli for transactivation of the ada promoter. 867 55

The evolution of the Metalloproteinase Disintegrin Cysteine-rich (MDC) gene family and that of the mammalian Matrix-degrading Metalloproteinases (MMPs) are compared. The alignment of snake venom and mammalian MDC and MMP precursor sequences generated a phylogenetic tree that grouped these proteins mainly according to their function. Based on this observation, a common ancestry is suggested for mammalian and snake venom MDCs; it is also possible that gene duplication of the already-assembled domain structure, followed by divergence of the copies, may have significantly contributed to the evolution of the functionally diverse MDC proteins. The data also suggest that the structural resemblance of the zinc-binding motif of venom MDCs and MMPs may best be explained by common ancestry and conservation of the proteolytic motifs during the divergence of the proteins rather than through convergent evolution.
J Mol Evol 1996 Sep
PMID:Evolution of disintegrin cysteine-rich and mammalian matrix-degrading metalloproteinases: gene duplication and divergence of a common ancestor rather than convergent evolution. 870 92

D-Penicillamine (beta, beta-dimethyl cysteine) is an antirheumatic thiol drug with a poorly understood mechanism of action. On the basis that gold(I) thiolates and D-penicillamine are both capable of forming stable bonds with endogenous thiols, we sought a common target of action. Cysteine residues in the basic DNA binding domains of Jun and Fos, members of the activator protein-1 (AP-1) transcription factor family, have been identified as likely targets for the therapeutic action of antirheumatic gold(I) thiolates. The current study demonstrates that AP-1 DNA binding is inhibited by D-penicillamine in the presence of Fenton reagents (Fe2+/EDTA and H2O2) but not with either agent alone. The effect is biphasic, with maximum inhibition in the concentration range of approximately 100-250 microM. Cysteine has qualitatively similar properties, although the effect is less pronounced. In contrast, glutathione and thiomalate do not inhibit AP-1 DNA binding, even in the presence of Fenton reagents. Mutant proteins were used to identify the cysteine residues within the DNA binding domains of Jun and Fos that are essential for the inhibitory action of D-penicillamine. The results suggest that D-penicillamine is distinguished from other thiols by its formation of sulfur-containing radicals capable of inhibiting AP-1 DNA binding by a mechanism involving the cysteine residues of Jun and Fos.
Mol Pharmacol 1996 Sep
PMID:D-penicillamine causes free radical-dependent inactivation of activator protein-1 DNA binding. 879 87

Proliferative growth of the ventricular myocyte (cardiomyocyte) is primarily limited to embryonic, fetal and very early neonatal periods of heart development. In contrast, cardiomyocyte maturation, as evidenced by cellular hypertrophy, is a long-term process that can occupy the bulk of the life-span of the mature organism. As the newborn myocyte undergoes a 'transition' from proliferative to hypertrophic growth, ventricular remodeling of the non-myocyte compartment is characterized by increased extracellular matrix (ECM) formation and coronary capillary angiogenesis. A role for ventricular-derived growth factors (GFs) in these inter-related processes are examined in an animal model of altered heart development produced by neonatal aortic banding. The suprarenal abdominal aorta of five day old rat pups were banded (B), sham operated (S), or untreated (C) and ventricular tissue (left ventricular free wall and septum) obtained at 7-, 14-, and 21-days post-intervention. Using Northern blot RNA hybridizations, expression of growth factors (GFs) and/or GF-receptors (GFR's) temporally associated with heart development were evaluated. Transcript levels for TGF-beta 1, IGF-II, and their associated cell surface receptors were increased in B animals. Concomitant changes in extracellular matrix (ECM) genes (as evaluated by Collagens Type I, III, and IV) were also increased in B animals. In addition, transcript levels for the vascular morphogenesis and remodeling-related protein SPARC (Secreted Protein, Acidic and Rich in Cysteine) was also elevated in the B animals. In several instances, S animals demonstrated changes in steady state transcript levels for genes which may influence myocyte maturation during the postnatal period. This suggests that normal autocrine/paracrine growth regulatory stimuli and responses can be modified (by surgical intervention and/or abdominal aortic banding) and these perturbations in gene expression may be related to previously documented changes in myocyte cell number, vascular composition, and ventricular architecture of the banded, neonatal heart. Future studies using this model will provide an opportunity to evaluate and possibly identify the stimuli and signal transduction machinery that regulate the final phases of myocyte proliferation, stimulate capillary formation and ECM deposition, and orchestrate the transition to hypertrophic growth during heart development.
Mol Cell Biochem
PMID:Immediate postnatal rat heart development modified by abdominal aortic banding: analysis of gene expression. 897 39

Cysteine and other thiol compounds can accelerate the unloading of nitric oxide (NO) from salivary nitrosyl-nitrophorins of the blood sucking bug Rhodnius prolixus. The dependence of NO unloading on cysteine concentration is biphasic, showing a maximum between 0.5 and 1 mM cysteine. The proposed mechanism of action for the unloading is a series of reactions where cysteine (at low concentrations) reacts with the heme group of nitrophorins to form cystine and superoxide. The superoxide then reacts with NO to form peroxynitrite, which decays to a mixture of nitrite and nitrate anions. At high cysteine concentrations, cysteine is converted to cystine and H2O and thus no removal of NO from nitrophorins is observed. The thiol oxidase activity of Rhodnius nitrophorins is similar to that observed before in plant peroxidases [Pichorner et al., Phytochemistry 31, 3371 (1992)]. The possible physiological significance of this reaction to probing and feeding by R. prolixus is discussed.
Insect Biochem Mol Biol
PMID:Salivary thiol oxidase activity of Rhodnius prolixus. 901 35

The complete coding sequence for the bovine thyrotropin (TSH) receptor was derived using a modified PCR cloning strategy. The bovine thyrotropin receptor conforms to the pattern of receptor interacting with membrane-bound G-protein already established in other species for TSH and gonadotropins receptors. The cDNA for the bovine TSH receptor consists of an open reading frame 2289 nucleotides in length, corresponding to a protein of 763 amino acids (estimated molecular mass of 86.4 kDa) which includes a 20 amino acid putative leading signal peptide. The receptor consists of a large NH2-terminal extracellular membrane domain of 417 amino acids with 5 potential N-linked glycosylation sites, a transmembrane domain (265 amino acids) consisting of 7 putative membrane alpha-helix spanning segments, and an intracytoplasmic COOH-terminal domain (82 amino acids). The bovine TSH receptor is one amino acid less than the corresponding sequence in dog, human, rat and mouse. Cysteine residues (n = 22) were conserved when compared with other TSH receptors. Three potential phosphorylation sites were found in the transmembrane domain and the COOH-terminal domain. As with other members of this receptor family, alternative splicing was observed. A transcribed but truncated TSH receptor of 1769 nucleotides was demonstrated, lacking half of the V segment of the transmembrane domain up to the COOH-terminal domain of the full length TSH receptor. Additionally, alternative transcriptional start sites were observed. Northern blot analysis using a probe (1170 bp) spanning part of the extracellular domain up to the first loop of the transmembrane domain showed specific expression in the bovine thyroid gland with major transcripts of 9.3 and 4.3 kb, and a minor transcript of 3.8 kb being detected.
J Mol Endocrinol 1997 Apr
PMID:Bovine thyrotropin receptor cDNA is characterized by full-length and truncated transcripts. 913 97

Cysteine proteinase cDNA fragment from adult mammalian trematode, Paragonimus westermani was amplified by reverse transcription-polymerase chain reaction (RT-PCR) using degenerate oligonucleotide primers derived from conserved cysteine proteinase sequences. The 5' and the 3' regions of the cysteine proteinase gene were amplified using the PCR protocol for the rapid amplification of cDNA ends (RACE). It has an open reading frame of 804 bp. The deduced amino acid sequence consists of 268 amino acids. Sequence analysis and alignment showed significant sequence similarity to other eukaryotic cysteine proteinases and conservation of the cysteine, histidine, and asparagine residues that form the catalytic triad. The cysteine proteinase cDNA fragment was also subcloned in the expression vector pET and expressed as a C-terminal His-tag fusion protein in Escherichia coli.
Mol Cells 1997 Jun 30
PMID:Cloning of a cysteine proteinase cDNA of adult Paragonimus westermani by polymerase chain reaction. 926 19

Oxidative inactivation of AMP deaminase and its protection were analyzed under the in situ conditions of yeast cells. AMP deaminase was readily inactivated by an exposure to hydrogen peroxide plus copper in permeabilized yeast cells. Addition of ascorbic acid further enhanced the inactivation of the enzyme, suggesting the hydroxyl radical produced by the Fenton reaction is responsible for the inactivation of the enzyme. Addition of histidine caused an effective protection against the inactivation of AMP deaminase by hydrogen peroxide-induced hydroxyl radical. The concentration of histidine required for half-maximal effect was within physiological range. Cysteine showed less effective protection against oxidative inactivation. Other amino acids as potent copper-chelating agents as well as trolox and taurine showed little or no effect. Histidine can act as a physiological "antioxidant" in yeast cells.
Biochem Mol Biol Int 1997 Aug
PMID:Protection by histidine against oxidative inactivation of AMP deaminase in yeast. 928 75

Cysteine proteinase isoforms, immunologically cross-reactive with cruzipain and with a similar apparent molecular mass, have been identified in epimastigotes of Trypanosoma cruzi by extraction and phase partition using the detergent Triton X-114. These isoforms are concentrated in the microsomal fraction obtained after differential centrifugation, which is known to consist essentially of plasma membrane, can be labelled by incubation of live parasites with sulfo-NHS-biotin, and bind to cystatin-sepharose affinity columns. They are present, albeit with a different electrophoretic pattern, in the epimastigote, amastigote and trypomastigote stages of the parasite.
Cell Mol Biol (Noisy-le-grand) 1998 May
PMID:Membrane-bound cysteine proteinase isoforms in different developmental stages of Trypanosoma cruzi. 962 Apr 48

Cysteine proteases play vital biological roles in both intracellular and extracellular environments. A cysteine protease migrating at 30 kDa was identified in somatic extracts of Toxocara canis larvae (TEX), by its binding to the biotinylated inhibitor Phe-Ala-CH2F. TEX proteases readily cleaved the cathepsin L- and B-specific peptide substrate Z-Phe-Arg-AMC and to a lesser extent, the cathepsin B-specific peptide Z-Arg-Arg-AMC. Excretory/secretory (TES) products of T. canis larvae did not cleave either substrate. Partial sequence encoding the 5' end of a cysteine protease cDNA from infective T. canis larvae was then obtained from an expressed sequence tag (EST) project. The entire cDNA (termed Tc-cpl-1) was subsequently sequenced and found to encode a preproenzyme similar to cathepsin L-like proteases (identities between 36 and 69%), the closest homologues being two predicted proteins from Caenorhabditis elegans cosmids, a cathepsin L-like enzyme from Brugia pahangi and a range of parasite and plant papain-like proteases. Sequence alignment with homologues of known secondary structure indicated several charged residues in the S1 and S2 subsites involved in determining substrate specificity. Some of these are shared with human cathepsin B, including Glu 205 (papain numbering), known to permit cleavage of Arg-Arg peptide bonds. The recombinant protease (rTc-CPL-1) was expressed in bacteria for immunisation of mice and the subsequent antiserum shown to specifically react with the 30 kDa native protease in TEX. Sera from mice infected with the parasite also contained antibodies to rTc-CPL-1 as did sera from nine patients with proven toxocariasis; control sera did not. Larger scale studies are underway to investigate the efficacy of rTc-CPL-1 as a diagnostic antigen for human toxocariasis, the current test for which relies on whole excretory/secretory antigens of cultured parasites.
Mol Biochem Parasitol 1998 May 01
PMID:Characterisation of Tc-cpl-1, a cathepsin L-like cysteine protease from Toxocara canis infective larvae. 965 32


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