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61.
Carbohydrate recognition by proteins is a key event in many biological
processes. Concanavalin A is known to specifically recognize the
pentasaccharide core (beta-GlcNAc-(1-->2)-alpha- Man-(1-->3)-[beta-
GlcNAc-(1-->2)-alpha-Man-(1-->6)]-Man) of N-linked oligosaccharides
with a Ka of 1.41 x 10(6 )M-1. We have determined the structure of
concanavalin A bound to beta-GlcNAc-(1-->2)-alpha-Man-(1-->3)-[beta-
GlcNAc-(1-->2)-alpha-Man- (1-->6)]-Man to 2.7A. In six of eight
subunits there is clear density for all five sugar residues and a well
ordered binding site. The pentasaccharide adopts the same conformation in
all eight subunits. The binding site is a continuous extended cleft on the
surface of the protein. Van der Waals interactions and hydrogen bonds
anchor the carbohydrate to the protein. Both GlcNAc residues contact the
protein. The GlcNAc on the 1-->6 arm of the pentasaccharide makes
particularly extensive contacts and including two hydrogen bonds. The
binding site of the 1-->3 arm GlcNAc is much less extensive.
Oligosaccharide recognition by Con A occurs through specific protein
carbohydrate interactions and does not require recruitment of adventitious
water molecules. The beta-GlcNAc-(1-->2)-Man glycosidic linkage PSI
torsion angle on the 1-->6 arm is rotated by over 50 degrees from that
observed in solution. This rotation is coupled to disruption of
interactions at the monosaccharide site. We suggest destabilization of the
monosaccharide site and the conformational strain reduces the free energy
liberated by additional interactions at the 1-->6 arm GlcNAc site.
相似文献
62.
A study was performed to determine whether the pressures routinely produced by bandaging for compression sclerotherapy of varicose veins are adequate to maintain the superfical veins almost empty of blood. The results suggest that well-applied bandages can provide sufficient support to combat the high distending pressures found in varicose veins. The large variation among different surgeons, however, indicates that any clinical assessment of compression sclerotherapy should include measurement of the pressure at which the bandages are applied. 相似文献
63.
Sandra Stefanovic‐Barrett Anna S Dickson Stephen P Burr James C Williamson Ian T Lobb Dick JH van den Boomen Paul J Lehner James A Nathan 《EMBO reports》2018,19(5)
Misfolded or damaged proteins are typically targeted for destruction by proteasome‐mediated degradation, but the mammalian ubiquitin machinery involved is incompletely understood. Here, using forward genetic screens in human cells, we find that the proteasome‐mediated degradation of the soluble misfolded reporter, mCherry‐CL1, involves two ER‐resident E3 ligases, MARCH6 and TRC8. mCherry‐CL1 degradation is routed via the ER membrane and dependent on the hydrophobicity of the substrate, with complete stabilisation only observed in double knockout MARCH6/TRC8 cells. To identify a more physiological correlate, we used quantitative mass spectrometry and found that TRC8 and MARCH6 depletion altered the turnover of the tail‐anchored protein heme oxygenase‐1 (HO‐1). These E3 ligases associate with the intramembrane cleaving signal peptide peptidase (SPP) and facilitate the degradation of HO‐1 following intramembrane proteolysis. Our results highlight how ER‐resident ligases may target the same substrates, but work independently of each other, to optimise the protein quality control of selected soluble and tail‐anchored proteins. 相似文献
64.
Catherine C Beauheim Farrell Wymore Michael Nitzberg Zachariah K Zachariah Heng Jin JH Pate Skene Catherine A Ball Gavin Sherlock 《BMC bioinformatics》2007,8(1):338
Background
Biomedical ontologies are being widely used to annotate biological data in a computer-accessible, consistent and well-defined manner. However, due to their size and complexity, annotating data with appropriate terms from an ontology is often challenging for experts and non-experts alike, because there exist few tools that allow one to quickly find relevant ontology terms to easily populate a web form. 相似文献65.
66.
Kirubhanand Chandrashekar Ponnulakshmi Rajagopal Shazia Fathima JH Saravanan Radhakrishnan Vijaya Prakash Krishnan Muthaiah Bharat Ramrao Sontakke Vishwajit Ravindra Deshmukh Vijayalakshmi Periyasamy Gayatri Girish Muthiyan Aaditya Madhusudan Tarnekar TS Gugapriya Patil Ashlesh Laxman Satyendra Chandra Tripathi Selvaraj Jayaraman 《Bioinformation》2021,17(10):866
Cissampelos pareira Linn. is a climbing herb known in Indian traditional medicine as laghupatha. It belongs to the Menispermaceae family. The enzyme glycogen phosphorylase (GP) is a promising target for the treatment of type-2 diabetes (T2DM). A variety of natural product inhibitors with both pharmaceutical and nutraceutical potential have been reported in the search for powerful, selective and drug-like GP inhibitors that could lead to hypoglycemic medicines. Therefore, it is of interest to document the molecular docking analysis data of glycogen phosphorylase with compounds from Cissampelos pareira Linn. We report the optimal binding features of 4 compounds namely Trans-N-feruloyltyramine, Coclaurine, Magnoflorine, and Curine with the target protein for further consideration in the context of T2DM. 相似文献
67.
A study has been made of changes in physical condition associated with bed rest and rehabilitation in hospital patients. It was found that after two weeks recumbent bed rest there was a significant decline in physical condition. It was also found that the better the initial physical condition the greater the decline. Rehabilitation was associated with an improvement in physical condition, which seemed to be related to the increased level of daily activity rather than to the absolute levels of physical condition. 相似文献
68.
69.
70.
Tineke E Buffart Melanie Louw Nicole CT van Grieken Marianne Tijssen Beatriz Carvalho Bauke Ylstra Heike Grabsch Chris JJ Mulder Cornelis JH van de Velde Schalk W van der Merwe Gerrit A Meijer 《BMC medical genomics》2011,4(1):7