Disease relevance of GCY

• Finally, GCY first became positive 2-3 mo prior to the onset of AGC on two patients, suggesting the possibility of identifying those at risk well before the onset of neutropenia [1].
• These results disclosed a wide Y long arm deletion, including all hypothized Yq azoospermia loci (except for AZFa and probably for one of the RBM genes, which lie proximally to the deletion) and possibly the Y-specific growth control region (GCY), mapped between DYS11 and DYS246 loci [2].
• To determine whether one or both of these two critical regions harbours GCY and whether one of the four genes assigned to the distal region is involved in determination of stature, nine adult patients with Yq chromosomal abnormalities were studied in detail [3].
• We report on a Japanese family affected by Emery-Dreifuss muscular dystrophy carrying a novel mutation of the emerin (STA) gene [4].
• STA was detected in F2/F7, CCRF-CEM, Molt-4, and CCRF-HSB (four human T ALL cell lines), in JURKAT (a human T cell leukemia line), and in MLA144 (a Gibbon T cell lymphoma line) [5].

Psychiatry related information on GCY

• A two-factor varimax solution yielded a first factor accounting for 49 per cent of total unrotated variance with high (0.70 to 0.91) loadings from Hallucinatory predisposition, Perceptual aberration, Schizophrenism, STA and STB scales, and was interpreted as reflecting a general factor of schizoid personality disorder [6].

High impact information on GCY

• At TS formation the 2' OH group of the P-site tRNA A76 forms a hydrogen bond with the oxygen atom of the carboxyl group of the amino acid attached to the A-site tRNA, which may be indicative of its catalytic role, consistent with recent biochemical experiments [7].
• The calculated TS activation energy, E(a), is 35.5 kcal (1 kcal = 4.18 kJ)/mol, and the increase in hydrogen bonding between the rotating A-site tRNA and ribosome nucleotides as the TS forms appears to stabilize it to a value qualitatively estimated to be approximately 18 kcal/mol [7].
• In Phi-value analysis, the effects of mutations on the folding kinetics are compared with the corresponding effects on thermodynamic stability to investigate the structure of the protein-folding transition state (TS) [8].
• In the conclusion, CHI's remarkable efficiency of stabilizing the TS and its relatively poor ability in organizing the ground state is compared with chorismate mutase whose catalytic prowess, when compared with water, originates predominantly from the enhanced NAC population at the active site [9].
• From the molecular dynamics simulations of apo-CHI, CHI complexed with CHN (CHI.CHN) and CHI.TS, we found: (i) Lys-97-general-acid catalysis of the O2'(-) nucleophilic addition; (ii) expulsion of three water molecules in the process of TS formation; (iii) release of enzyme structural distortion on TS formation [9].

Chemical compound and disease context of GCY

• In general, serum levels of IGF system components showed a significant positive correlation to bone density in TS II and III girls, whereas bone resorption markers corrected for creatinine showed a significant negative correlation to bone density in TS III and IV girls [10].
• In conclusion, in the majority of HT58 lymphoma cells the apoptotic machinery is "primed" (the components are already expressed) and ETO-induced apoptosis is regulated by STA sensitive phosphorylation and proteolysis by cystein proteases, but not affected by ADP-ribozylation or p53 [11].

Biological context of GCY

• Molecular analysis of the Yq arm of the translocation chromosome revealed the presence of markers DYS273 to DYS246 harboring the hypothesized growth control gene critical region (GCY) on Yq, thereby placing the deletion breakpoint between markers DYS11 and DYS273 [12].
• Our analysis focuses on the facts that (i) a low-barrier hydrogen bond is less stable than a regular hydrogen bond in water, (ii) TSs are more stable in the enzyme active sites than in water, and (iii) a nonpolar active site would destabilize the TS relative to its energy in water [13].
• Serum levels of interleukin-6 were decreased during late puberty and were negatively correlated with bone density in TS III and IV girls [10].
• We discuss the potential of direct calculations of binding energy of the TS in a rational design of TS analogues and in drug design [14].
• INTERVENTIONS: All patients were screened daily for lupus anticoagulants with the activated partial thromboplastin time STA assay [15].

Anatomical context of GCY

• Granulocyte antigens detected by cytotoxicity (GCY) and capillary agglutination (CAN) [16].
• Thus, STA appears to be a cytoplasmic marker for activated T cells [5].
• K-1-21 was unexpectedly shown to bind to a determinant, STA (Sezary T cell antigen), detected by immunofluorescence in the cytoplasm but not on the surface of Sezary T cells isolated from peripheral blood (4/4 cases) and in Sezary T cells from lymph node and bone marrow (one patient) [5].
• The incidence of nerve structures in the PA adventitio-medial junction was only 3% of those in the STA, and these were situated more than 3 microm from the closest smooth muscle cell [17].
• It was determined that although ecTS is as stable as human TS (hTS) in transfected mammalian cells, ecTS is produced at only 40% the level of hTS, indicating poor translation of ecTS in eukaryotic cells [18].

Associations of GCY with chemical compounds

• STA from radiolabeled MLA144 cell lysates was immunoprecipitated by K-1-21 and was identified on polyacrylamide gel electrophoresis under reducing conditions as a protein of m.w. 57,000 [5].
• STA has a high content of sugar, most of which is L-arabinose, and is rich in Hyp and Cys [19].
• We propose that protein-facilitated dynamic modes in hPNP cause this stack, centered on the ribosyl O-4' oxygen, to squeeze together and push electrons toward the purine ring, stabilizing the oxacarbenium character of the TS [20].
• Thus, the reaction occurs faster in water than in methanol due to greater stabilization of the TS in water by specific interactions with first shell solvent molecules [21].
• The geometrical complimentarity of the organized enzyme structure to the TS structure is a result of preferential binding of the proline N and the amide carbonyl of the TS compared to that of GS [22].

Regulatory relationships of GCY

• It further possibly allowed to relate the GCY gene(s) to the control of GH or IGF-I receptor or post-receptor pathway, being the alteration of this gene(s) consistent with the hormonal pattern of the patient [2].

Other interactions of GCY

• These results suggest that the Y-specific growth gene GCY on Yq compensates for the missing growth gene SS on Xp22.3 [12].
• Case 1 also had deletion of the putative growth controlling gene (GCY) and the Yq breakpoint was located between sY741 and USP9Y [23].

Analytical, diagnostic and therapeutic context of GCY

• Initial mapping assignments to narrow down the localization of the Y chromosome growth-control gene, GCY, were based on molecular analysis of patients carrying a 46,XYq- karyotype as defined by classic karyotyping [24].
• Cytoplasmic inhibition immunofluorescence studies indicated that K-1-21 binding to STA in Sezary cells or T cell lines was inhibited by preincubation of the K-1-21 antibody with purified kappa-Bence Jones protein [5].
• Potato lectin (Solanum tuberosum agglutinin, STA), purified by affinity chromatography on tri-N-acetylchitotriose-Sepharose 6B, has Mr approximately 100,000, as estimated by gel filtration on Sephadex G-150 and is an aggregating system with a monomer Mr = 54,000, as estimated by sedimentation equilibrium analysis [19].
• Specifically, we present herein a protein engineering study combining classic truncation (Ala/Gly) and atypical mutants to predict folding TS ensemble properties [25].
• A quantitative evaluation of the bypass was attempted by determining the STA blood flow velocity and pattern [26].

References