Evidence for Subdomain Flexibility in Drosophila melanogaster Acetylcholinesterase Export

@article{citeulike:2943645, abstract = {Abstract: The catalytic domain of the acetylcholinesterases is composed of a single polypeptide chain, the folding of which determines two subdomains. We have linked these two subdomains by mutating two residues, I327 and D375, to cysteines, to form a disulfide bridge. As a consequence, the hydrodynamic radius of the protein was reduced, suggesting that there is some flexibility in the subdomain connection. In addition to the smaller size, the mutated protein is more stable than the wild-type protein. Therefore, the flexibility between the two domains is a weak point in terms of protein stability. As expected from the location of the disulfide bond at the rim of the active site, the kinetic studies show that it affects interactions with peripheral ligands and the entrance of some of the bulkier substrates, like o-nitrophenyl acetate. In addition, the mutations affect the catalytic step for o-nitrophenyl acetate and phosphorylation by organophosphates, suggesting that this movement between the two subdomains is connected with the cooperativity between the peripheral and catalytic sites.}, address = {Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia, and IPBS-CNRS, 205 Route de Narbonne, Toulouse, France}, author = {Stojan, Jure and Ladurantie, Caroline and Siadat, Omid R. and Paquereau, Laurent and Fournier, Didier}, citeulike-article-id = {2943645}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/bi7025479}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/bi7025479}, day = {20}, doi = {10.1021/bi7025479}, journal = {Biochemistry}, keywords = {acetylcholinesterase, allostery}, month = {May}, number = {20}, pages = {5599--5607}, posted-at = {2008-06-30 11:35:00}, priority = {0}, title = {Evidence for Subdomain Flexibility in Drosophila melanogaster Acetylcholinesterase}, url = {http://dx.doi.org/10.1021/bi7025479}, volume = {47}, year = {2008} }

TY - JOUR ID - citeulike:2943645 L3 - citeulike-article-id:2943645 N2 - Abstract: The catalytic domain of the acetylcholinesterases is composed of a single polypeptide chain, the folding of which determines two subdomains. We have linked these two subdomains by mutating two residues, I327 and D375, to cysteines, to form a disulfide bridge. As a consequence, the hydrodynamic radius of the protein was reduced, suggesting that there is some flexibility in the subdomain connection. In addition to the smaller size, the mutated protein is more stable than the wild-type protein. Therefore, the flexibility between the two domains is a weak point in terms of protein stability. As expected from the location of the disulfide bond at the rim of the active site, the kinetic studies show that it affects interactions with peripheral ligands and the entrance of some of the bulkier substrates, like o-nitrophenyl acetate. In addition, the mutations affect the catalytic step for o-nitrophenyl acetate and phosphorylation by organophosphates, suggesting that this movement between the two subdomains is connected with the cooperativity between the peripheral and catalytic sites. IS - 20 JF - Biochemistry AD - Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia, and IPBS-CNRS, 205 Route de Narbonne, Toulouse, France EP - 5607 TI - Evidence for Subdomain Flexibility in Drosophila melanogaster Acetylcholinesterase VL - 47 SP - 5599 KW - acetylcholinesterase KW - allostery AU - Stojan, Jure AU - Ladurantie, Caroline AU - Siadat, Omid AU - Paquereau, Laurent AU - Fournier, Didier PY - 2008/05/20/ UR - http://dx.doi.org/10.1021/bi7025479 ER -