The Experts below are selected from a list of 222 Experts worldwide ranked by ideXlab platform
Qingmin Man - One of the best experts on this subject based on the ideXlab platform.
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investigation of the remote Acyl Group participation in glycosylation from conformational perspectives by using trichloroacetimidate as the acetyl surrogate
Organic chemistry frontiers, 2020Co-Authors: Qingmin Man, Yang Zhang, Jia Guo, Yichu Liu, Yueyue Zhu, Mingyue Zheng, Ning DingAbstract:Unlike the O2 neighboring Group participation in glycosylation, the participating effect of esters located on more remote positions of glycopyranosyl donors has not been unambiguously established and provokes plenty of questions. Here we systematically trapped the participation intermediates on three common pyranoses based on a ‘bis-trichloroacetimidates method’, which showed that trichloroacetimidate Group participations from O4 and O6 are all quite possible except for D-mannopyranosyl O4. Besides, with the trapped participation intermediates in hand, the NMR data was collected to assist the DFT calculations to build up the most possible participating conformations, which, in turn, predicted the potentials of remote participation by trichloroacetimidates at different positions on the same donor. Finally, the ‘tris-trichloroacetimidates method’ was employed to support the computational calculations. This work provided a conformational perspective on understanding the potent remote Acyl Group participation in glycosylation reaction.
Alexander M Dizhoor - One of the best experts on this subject based on the ideXlab platform.
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calcium myristoyl tug is a new mechanism for intramolecular tuning of calcium sensitivity and target enzyme interaction for guanylyl cyclase activating protein 1 dynamic connection between n fatty Acyl Group and ef hand controls calcium sensitivity
Journal of Biological Chemistry, 2012Co-Authors: Igor V. Peshenko, Elena V Olshevskaya, Sunghyuk Lim, James B. Ames, Alexander M DizhoorAbstract:Guanylyl cyclase-activating protein 1 (GCAP1), a myristoylated Ca2+ sensor in vision, regulates retinal guanylyl cyclase (RetGC). We show that protein-myristoyl Group interactions control Ca2+ sensitivity, apparent affinity for RetGC, and maximal level of cyclase activation. Mutating residues near the myristoyl moiety affected the affinity of Ca2+ binding to EF-hand 4. Inserting Phe residues in the cavity around the myristoyl Group increased both the affinity of GCAP1 for RetGC and maximal activation of the cyclase. NMR spectra show that the myristoyl Group in the L80F/L176F/V180F mutant remained sequestered inside GCAP1 in both Ca2+-bound and Mg2+-bound states. This mutant displayed much higher affinity for the cyclase but reduced Ca2+ sensitivity of the cyclase regulation. The L176F substitution improved affinity of myristoylated and non-Acylated GCAP1 for the cyclase but simultaneously reduced the affinity of Ca2+ binding to EF-hand 4 and Ca2+ sensitivity of the cyclase regulation by Acylated GCAP1. The replacement of amino acids near both ends of the myristoyl moiety (Leu80 and Val180) minimally affected regulatory properties of GCAP1. N-Lauryl- and N-myristoyl-GCAP1 activated RetGC in a similar fashion. Thus, protein interactions with the central region of the fatty Acyl chain optimize GCAP1 binding to RetGC and maximize activation of the cyclase. We propose a dynamic connection (or “tug”) between the fatty Acyl Group and EF-hand 4 via the C-terminal helix that attenuates the efficiency of RetGC activation in exchange for optimal Ca2+ sensitivity.
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Calcium-myristoyl Tug is a new mechanism for intramolecular tuning of calcium sensitivity and target enzyme interaction for guanylyl cyclase-activating protein 1: dynamic connection between N-fatty Acyl Group and EF-hand controls calcium sensitivity.
The Journal of biological chemistry, 2012Co-Authors: Igor V. Peshenko, Elena V Olshevskaya, Sunghyuk Lim, James B. Ames, Alexander M DizhoorAbstract:Abstract Guanylyl cyclase activating protein 1 (GCAP1), a myristoylated Ca2+ sensor in vision, regulates retinal guanylyl cyclase (RetGC). We show that protein-myristoyl Group interactions control Ca2+ sensitivity, apparent affinity for RetGC, and maximal level of cyclase activation. Mutating residues near the myristoyl moiety affects the affinity of Ca2+ binding to EF-hand 4. Inserting Phe residues in the cavity around the myristoyl Group increases both the affinity of GCAP1 for RetGC and maximal activation of the cyclase. NMR spectra show that the myristoyl Group in the L80F/L176F/V180F mutant remains sequestered inside GCAP1 in both Ca2+-bound and Mg2+-bound states. This mutant displayed much higher affinity for the cyclase but reduced Ca2+ sensitivity of the cyclase regulation. The L176F substitution improved affinity of myristoylated and non-Acylated GCAP1 for the cyclase, but simultaneously reduced the affinity of Ca2+ binding to EF-hand 4 and Ca2+-sensitivity of the cyclase regulation by Acylated GCAP1. The replacement of amino acids near both ends of the myristoyl moiety (Leu80 and Val 180) minimally affected regulatory properties of GCAP1. N-lauryl- and N-myristoyl-GCAP1 activated RetGC in a similar fashion. Thus, protein interactions with the central region of the fatty Acyl chain optimize GCAP1 binding to RetGC and maximize activation of the cyclase. We propose a dynamic connection (or 'tug') between the fatty Acyl Group and EF-hand 4 via the C-terminal helix that attenuates the efficiency of RetGC activation in exchange for optimal Ca2+ sensitivity.
Ning Ding - One of the best experts on this subject based on the ideXlab platform.
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investigation of the remote Acyl Group participation in glycosylation from conformational perspectives by using trichloroacetimidate as the acetyl surrogate
Organic chemistry frontiers, 2020Co-Authors: Qingmin Man, Yang Zhang, Jia Guo, Yichu Liu, Yueyue Zhu, Mingyue Zheng, Ning DingAbstract:Unlike the O2 neighboring Group participation in glycosylation, the participating effect of esters located on more remote positions of glycopyranosyl donors has not been unambiguously established and provokes plenty of questions. Here we systematically trapped the participation intermediates on three common pyranoses based on a ‘bis-trichloroacetimidates method’, which showed that trichloroacetimidate Group participations from O4 and O6 are all quite possible except for D-mannopyranosyl O4. Besides, with the trapped participation intermediates in hand, the NMR data was collected to assist the DFT calculations to build up the most possible participating conformations, which, in turn, predicted the potentials of remote participation by trichloroacetimidates at different positions on the same donor. Finally, the ‘tris-trichloroacetimidates method’ was employed to support the computational calculations. This work provided a conformational perspective on understanding the potent remote Acyl Group participation in glycosylation reaction.
Papasani V. Subbaiah - One of the best experts on this subject based on the ideXlab platform.
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Modulation of the positional specificity of lecithin-cholesterol Acyltransferase by the Acyl Group composition of its phosphatidylcholine substrate: role of the sn-1-Acyl Group.
Biochemistry, 1998Co-Authors: Ming Liu, Veedamali S. Subramanian, Papasani V. SubbaiahAbstract:Human lecithin-cholesterol Acyltransferase (LCAT), which is normally specific for the sn-2 position of phosphatidylcholine (PC), derives a significant percentage of Acyl Groups from the sn-1 position, when sn-2 is occupied by 18:0, 20:4, or 22:6. We investigated the relative importance of the two Acyl Groups of PC in determining the positional specificity by first analyzing the cholesteryl esters formed in the presence of symmetric PCs labeled at sn-2. Both human and rat LCATs transferred exclusively the sn-2-Acyl Group from all symmetric PCs, including 18:0-18:0, and 20:4-20:4, showing that the presence of these fatty acids at sn-2 does not automatically alter the positional specificity. The role of the sn-1-Acyl Group was then tested by using PCs containing 20:4 or 18:0 at sn-2 and fatty acids of various chain lengths and unsaturation at sn-1. With 20:4 at sn-2 and saturated fatty acids of various chain lengths at sn-1, human and rat LCATs derived, respectively, 5-72% and 1-20% of the total Acyl Groups from the sn-1 position. However, the chain length of the sn-1-Acyl did not correlate with its utilization by either enzyme. Various unsaturated fatty acids at sn-1 also were transferred by human LCAT at a higher rate (5-75% of total) than they were transferred by rat LCAT (0-21%). With sn-2-18:0 PCs, however, rat LCAT exhibited greater alteration in positional specificity (30-95% from sn-1) than human LCAT (15-83% from sn-1). These results show that while the primary determinant of positional specificity is the sn-2-Acyl Group of PC, the structure of sn-1-Acyl significantly modifies it.
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Role of sn-2 Acyl Group of phosphatidylcholine in determining the positional specificity of lecithin-cholesterol Acyltransferase.
Biochemistry, 1994Co-Authors: Papasani V. Subbaiah, Ming Liu, Fritz PaltaufAbstract:Although human plasma lecithin-cholesterol Acyltransferase (LCAT) is believed to be specific for the sn-2 position of phosphatidylcholine (PC), our recent studies showed that it derives a significant percent of Acyl Groups from the sn-1 position of certain PC species. To understand the physicochemical basis for this altered positional specificity, we determined the effect of sn-2 Acyl Group of PC on the enzyme activity and utilization of 16:0 from the sn-1 position by purified human and rat LCATs. Positional isomers of PC containing 16:0 at sn-2 were better substrates for human LCAT than the corresponding sn-1-16:0 isomers, whereas the reverse was true for rat LCAT. The positional specificity of human LCAT varied greatly depending on the nature of the Acyl Group at sn-2. The sn-1 contribution from various sn-1-16:0-2-Acyl PCs for cholesteryl ester (CE) synthesis was 1.0% from 16:0-16:0, 1.4% from 16:0-20:5, 7.3% from 16:0-18:1, 47.0% from 16:0-20:3, 49.9% from 16:0-20:4, 54.9% from 16:0-22:6, and 72.3% from 16:0-18:0. There was a linear relationship between the percentage of 16:0 CE formed (from sn-1 position) and the Acyl chain length at sn-2 position (r = 0.94). Rat LCAT also transferred some 16:0 from sn-1 position of 16:0-22:6, 16:0-20:3, and 16:0-18:0 PCs, but not from the other natural PCs tested. The phospholipase A activity of both LCATs in the presence of 16:0-20:4 PC showed the same positional specificity as CE synthesis, indicating that the specificity is determined at the formation of Acyl-enzyme intermediate. These results show that the positional specificity of LCAT is influenced by the structure of PC, especially the chain length of the sn-2 Acyl Group.
Yichu Liu - One of the best experts on this subject based on the ideXlab platform.
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investigation of the remote Acyl Group participation in glycosylation from conformational perspectives by using trichloroacetimidate as the acetyl surrogate
Organic chemistry frontiers, 2020Co-Authors: Qingmin Man, Yang Zhang, Jia Guo, Yichu Liu, Yueyue Zhu, Mingyue Zheng, Ning DingAbstract:Unlike the O2 neighboring Group participation in glycosylation, the participating effect of esters located on more remote positions of glycopyranosyl donors has not been unambiguously established and provokes plenty of questions. Here we systematically trapped the participation intermediates on three common pyranoses based on a ‘bis-trichloroacetimidates method’, which showed that trichloroacetimidate Group participations from O4 and O6 are all quite possible except for D-mannopyranosyl O4. Besides, with the trapped participation intermediates in hand, the NMR data was collected to assist the DFT calculations to build up the most possible participating conformations, which, in turn, predicted the potentials of remote participation by trichloroacetimidates at different positions on the same donor. Finally, the ‘tris-trichloroacetimidates method’ was employed to support the computational calculations. This work provided a conformational perspective on understanding the potent remote Acyl Group participation in glycosylation reaction.
