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排序方式: 共有98条查询结果,搜索用时 15 毫秒
1.
Yongbo Hu Erin Webb Jasbir Singh Barry A Morgan James A Gainor Thomas D Gordon Teruna J Siahaan 《The Journal of biological chemistry》2002,277(10):8366-8371
The molecular basis of the substrate specificity of Clostridium histolyticum beta-collagenase was investigated using a combinatorial method. An immobilized positional peptide library, which contains 24,000 sequences, was constructed with a 7-hydroxycoumarin-4-propanoyl (Cop) fluorescent group attached at the N terminus of each sequence. This immobilized peptide library was incubated with C. histolyticum beta-collagenase, releasing fluorogenic fragments in the solution phase. The relative substrate specificity (k(cat)/K(m)) for each member of the library was determined by measuring fluorescence intensity in the solution phase. Edman sequencing was used to assign structure to subsites of active substrate mixtures. Collectively, the substrate preference for subsites (P(3)-P(4)') of C. histolyticum beta-collagenase was determined. The last position on the C-terminal side in which the identity of the amino acids affects the activity of the enzyme is P(4)', and an aromatic side chain is preferred in this position. The optimal P(1)'-P(3)' extended substrate sequence is P(1)'-Gly/Ala, P(2)'-Pro/Xaa, and P(3)'-Lys/Arg/Pro/Thr/Ser. The Cop group in either the P(2) or P(3) position is required for a high substrate activity with C. histolyticum beta-collagenase. S(2) and S(3) sites of the protease play a dominant role in fixing the substrate specificity. The immobilized peptide library proved to be a powerful approach for assessing the substrate specificity of C. histolyticum beta-collagenase, so it may be applied to the study of other proteases of interest. 相似文献
2.
The husk from the seeds of Plantago ovata Forsk yielded two fractions when exposed to mild aikali, namely, the mucilage polysaccharide (85%, apparently a single species) and the non-polysaccharide component (15%). Methylation analysis and partial hydrolysis with acid showed the mucilage polysaccharide to be a highly branched, acidic arabinoxylan, the xylan backbone having both (1→4) and (1→3) linkages. The majority of the residues in the xylan backbone are variously substituted at O-2 and O-3 with arabinose, xylose, and an aldobiouronic acid identified as 2-O-(galactopyranosyluronic acid)-rhamnose. A structure incorporating these features for the husk polysaccharide is proposed. 相似文献
3.
Kumar Vikas Singh Jaswinder Bala Kiran Singh Jasbir 《Molecular biology reports》2020,47(12):9489-9497
Molecular Biology Reports - Insulin resistance may become the most powerful predictor of future development of type 2 diabetes mellitus (T2DM) and a therapeutic target for the treatment of the... 相似文献
4.
Kaustuv Basu Nancy Maurya Jasbir Kaur Rohit Saxena Viney Gupta Ramanjit Sihota Ilora Ghosh 《Cell biology international》2019,43(7):820-834
The pathological mechanism underlying glaucoma has always been a complex aspect of this permanently blinding disease but proteomic studies have been helpful in elucidating it to a great extent in several studies. This study was designed to evaluate the expression and to get an idea about the function of two novel markers (ligatin and fibulin‐7) identified in human aqueous humor (hAH) in relation to glaucomatous progression. A significant increase in the protein content of glaucomatous hAH compared to that of non‐glaucomatous controls (NG‐Ctrls) was observed. Ligatin, fibulin‐7, and its proteolysis were revealed in hAH of primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG) and NG‐Ctrls. Quantification confirmed no significant difference in expression of ligatin, whereas fibulin‐7 was significantly (P < 0.05) low in hAH of PACG in comparison to NG‐Ctrls and POAG. Importantly the immunohistochemical assay for both indicated their possible involvement in the maintenance of the appropriate structure of TM in vivo. Since oxidative stress is a major contributor to glaucomatous pathogenesis, in vitro analysis of nuclear and cytoplasmic fractions indicated intracellular changes in localization and expression of ligatin upon oxidative insult of human trabecular meshwork (TM) cells. While no such changes were found for fibulin‐7 expression. This was also corroborated with the immunocytochemical assay. Though a study with a small sample size, this is the first report which confirms the presence of ligatin and fibulin‐7 in hAH, quantified their differential expression, and indicated the possibility of their involvement in the maintenance of the TM structure. 相似文献
5.
Maninder Kaur Yogesh Vikal Harleen Kaur Lalit Pal Kirandeep Kaur Jasbir Singh Chawla 《Journal of Phytopathology》2019,167(10):591-600
Southern leaf blight (SLB) caused by the fungus Cochliobolus heterostrophus (Drechs.) Drechs. is a major foliar disease of maize worldwide. Our objectives were to identify quantitative trait loci (QTL) for resistance to SLB and flowering traits in recombinant inbred line (RIL) population derived from the cross of inbred lines LM5 (resistant) and CM140 (susceptible). A set of 207 RILs were phenotyped for resistance to SLB at three time intervals for two consecutive years. Four putative QTL for SLB resistance were detected on chromosomes 3, 8 and 9 that accounted for 54% of the total phenotypic variation. Days to silking and anthesis–silking interval (ASI) QTL were located on chromosomes 6, 7 and 9. A comparison of the obtained results with the published SLB resistance QTL studies suggested that the detected bins 9.03/02 and 8.03/8.02 are the hot spots for SLB resistance whereas novel QTL were identified in bins 3.08 and 8.01/8.04. The linked markers are being utilized for marker‐assisted mobilization of QTL conferring resistance to SLB in elite maize backgrounds. Fine mapping of identified QTL will facilitate identification of candidate genes underlying SLB resistance. 相似文献
6.
7.
Juggi JS 《Journal of cellular and molecular medicine》2002,6(4):621-630
This paper aims to study of the effects of ischemia‐reperfusion on the post‐rest inotropy and to characterize post‐rest B1:B2 ratio as an index of intracellular Ca2+ overload. When the rest interval between the cardiac beats is increased, the magnitude of the post‐rest beats is increased. First beat (B1) is maximally potentiated with exponental decline of the second (B2) and subsequent beats, thereby establishing a normal B1:B2 ratio of post‐ rest inotropy of the cardiac muscle. The rest potentiation of B1 and subsequent decay in the magnitude B2 is thought to develop from the time‐dependent changes in the Ca2+‐uptake and release from the sarcoplasmic reticulum (SR). Ca2+‐kinetics of SR can be modulated by a variety of interventions which produce Ca2+ loading of the SR. Methods: Isolated perfused (K‐H buffer, 34°C) rat hearts were paced at 1 Hz (steady state frequency). Interbeat intervals between 1s and 10s were introduced and the recovery in the left ventricular contractile force (Pmax) of post‐rest B1 and B2 for each interval was recorded. Their relative relationship was computed and compared under control and experimental conditions. Results: High extracellular Ca2+ (2.50 to 7.0 mM) or low extracellular Na+ (50% of control), and ischemia (60 min, 34°C) ‐ reperfusion (30 min, 34°C) caused the reversal of the control relationship of the B1 to B2, with B2 being more potentiated than B1, accompanied by the appearance of after‐contractions during the rest intervals of 4s or more. The mean (± SE) control B1:B2 ratio (at 4s interval) of 1.12 ± 0.05 was significantly (P<0.001) reduced to 0.93 ± 0.07; 0.89 ± 0.01; and 0.96 ± 0.02 after high Ca2+ (6 mM) perfusion, low Na+(50%) perfusion and ischemia‐reperfusion respectively. Simultaneous perfusion with ryanodine (1 μM) abolished the after‐contractions and significantly increased the reduced ratios. The time course of changes in B1:B2 ratio after graded ischemia‐reperfusion showed a significant fall in the ratio between 30 and 60 min of ischemia. A parallel change in Pmax and a significant rise in the left ventricular end‐diastolic pressure, indicating an irreversible phase of the injury was recorded. No significant changes in B1:B2 ratio were detected during the reversible phase (<30 min) of the ischemia‐reperfusion injury. Conclusions: Ischemia‐reperfusion induces significant alterations in the relative ratio of the post‐rest contractions of the left ventricle in isolated perfused rat heart. The altered ratios were characterized to predict the irreversibility of the reperfusion injury and to index the extent of Ca2+‐loading of the sarcoplasmic reticulum. 相似文献
8.
Nian Zhou Alexandre M. Polozov Matthew O’Connell James Burgeson Peng Yu Wayne Zeller Jun Zhang Emmanuel Onua Jose Ramirez Gudrun A. Palsdottir Gudrun V. Halldorsdottir Thorkell Andresson Alex S. Kiselyov Mark Gurney Jasbir Singh 《Bioorganic & medicinal chemistry letters》2010,20(8):2658-2664
A series of novel 1,7-disubstituted oxyindoles were shown to be potent and selective EP3 receptor antagonists. Variation of substitution pattern at the C-3 position of indole enhanced in vitro metabolic stability of the resulting derivatives. Series 27a–c showed >1000-fold selectivity over a panel of prostanoid receptors including IP, FP, EP1, EP2 and EP4. These agents also featured low CYP inhibition and good activity in the functional rat platelet aggregation assay. 相似文献
9.
Specificity and Structure of a High Affinity Activin Receptor-like Kinase 1 (ALK1) Signaling Complex
Townson SA Martinez-Hackert E Greppi C Lowden P Sako D Liu J Ucran JA Liharska K Underwood KW Seehra J Kumar R Grinberg AV 《The Journal of biological chemistry》2012,287(33):27313-27325
Activin receptor-like kinase 1 (ALK1), an endothelial cell-specific type I receptor of the TGF-β superfamily, is an important regulator of normal blood vessel development as well as pathological tumor angiogenesis. As such, ALK1 is an important therapeutic target. Thus, several ALK1-directed agents are currently in clinical trials as anti-angiogenic cancer therapeutics. Given the biological and clinical importance of the ALK1 signaling pathway, we sought to elucidate the biophysical and structural basis underlying ALK1 signaling. The TGF-β family ligands BMP9 and BMP10 as well as the three type II TGF-β family receptors ActRIIA, ActRIIB, and BMPRII have been implicated in ALK1 signaling. Here, we provide a kinetic and thermodynamic analysis of BMP9 and BMP10 interactions with ALK1 and type II receptors. Our data show that BMP9 displays a significant discrimination in type II receptor binding, whereas BMP10 does not. We also report the crystal structure of a fully assembled ternary complex of BMP9 with the extracellular domains of ALK1 and ActRIIB. The structure reveals that the high specificity of ALK1 for BMP9/10 is determined by a novel orientation of ALK1 with respect to BMP9, which leads to a unique set of receptor-ligand interactions. In addition, the structure explains how BMP9 discriminates between low and high affinity type II receptors. Taken together, our findings provide structural and mechanistic insights into ALK1 signaling that could serve as a basis for novel anti-angiogenic therapies. 相似文献
10.
A dipeptidyl peptidase (DPP) from goat brain has been purified. The purified enzyme showed a single band on sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). It is a monomer with molecular weight of 69kDa with a pI of 4.5. The K(m) was estimated to be 39microM for Arg-Arg-4-methoxy-beta-naphthylamide (Arg-Arg-4mbetaNA). This enzyme is strongly inhibited by commonly used metallochelators and sulfhydryl reagents. Among various beta-naphthylamides examined, Arg-Arg-4mbetaNA was the most rapidly hydrolyzed substrate. Although, initially it was thought to be the DPP-III but on the basis of its molecular weight and inhibition studies, it was concluded that this enzyme is a functional homologue of DPP-III. 相似文献