Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroligins (NLs) are a family of transmembrane proteins that function in synapse formation and/or remodeling by interacting with beta-neurexins (beta-NXs) to form heterophilic cell adhesions. The large N-terminal extracellular domain of NLs, required for beta-NX interactions, has sequence homology to the alpha/beta hydrolase fold superfamily of proteins. By peptide mapping and mass spectrometric analysis of a soluble recombinant form of NL1, several structural features of the extracellular domain have been established. Of the nine cysteine residues in NL1, eight are shown to form intramolecular disulfide bonds. Disulfide pairings of Cys 117 to Cys 153 and Cys 342 to Cys 353 are consistent with disulfide linkages that are conserved among the family of alpha/beta hydrolase proteins. The disulfide bond between Cys 172 and Cys 181 occurs within a region of the protein encoded by an alternatively spliced exon. The disulfide pairing of Cys 512 and Cys 546 in NL1 yields a structural motif unique to the NLs, since these residues are highly conserved. The potential N-glycosylation sequons in NL1 at Asn 109, Asn 303, Asn 343, and Asn 547 are shown occupied by carbohydrate. An additional consensus sequence for N-glycosylation at Asn 662 is likely occupied. Analysis of N-linked oligosaccharide content by mass matching paradigms reveals significant microheterogeneous populations of complex glycosyl moieties. In addition, O-linked glycosylation is observed in the predicted stalk region of NL1, prior to the transmembrane spanning domain. From predictions based on sequence homology of NL1 to acetylcholinesterase and the molecular features of NL1 established from mass spectrometric analysis, a novel topology model for NL three-dimensional structure has been constructed.
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PMID:Structural characterization of recombinant soluble rat neuroligin 1: mapping of secondary structure and glycosylation by mass spectrometry. 1476 26

The neuroligins are postsynaptic cell adhesion proteins whose extracellular domain belongs to the alpha/beta-hydrolase fold family of proteins, a family characterized through the enzyme acetylcholinesterase (AChE) and other enzymes with various substrate specificities. Neuroligin associations with the pre-synaptic neurexins participate in synapse maturation and maintenance. Alternative splicing of the neuroligin and neurexin genes results in multiple isoforms and presumably regulation of activity, while mutations appear to be associated with autism spectrum disorders. The crystal structures of the extracellular, cell adhesion domain of three neuroligins (NL1, NL2 and NL4) revealed features that distinguish the neuroligins from their enzyme relatives and could not be predicted by homology modelling from an AChE template. The structures of NL1 and NL4 bound with a soluble beta-neurexin domain (Nrxbeta1) revealed the precise position and orientation of the bound Nrxbeta1 and the Ca(2+)-dependent interaction network at the complex interface. Herein we present an overview of the unbound and Nrxbeta1-bound neuroligin structures and compare them with structures of AChEs with and without a bound fasciculin partner. This study exemplifies how an alpha/beta-hydrolase fold domain tailored for catalysis varies to acquire adhesion properties, and defines three surface regions with distinctive locations and properties for homologous or heterologous partner association.
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PMID:Structure-function relationships of the alpha/beta-hydrolase fold domain of neuroligin: a comparison with acetylcholinesterase. 2010 Apr 70