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http://purl.uniprot.org/citations/16540464http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16540464http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16540464http://www.w3.org/2000/01/rdf-schema#comment"Congenital disorder of glycosylation type 1a (CDG-1a) is a congenital disease characterized by severe defects in nervous system development. It is caused by mutations in alpha-phosphomannomutase (of which there are two isozymes, alpha-PMM1 and alpha-PPM2). Here we report the x-ray crystal structures of human alpha-PMM1 in the open conformation, with and without the bound substrate, alpha-D-mannose 1-phosphate. Alpha-PMM1, like most haloalkanoic acid dehalogenase superfamily (HADSF) members, consists of two domains, the cap and core, which open to bind substrate and then close to provide a solvent-exclusive environment for catalysis. The substrate phosphate group is observed at a positively charged site of the cap domain, rather than at the core domain phosphoryl-transfer site defined by the Asp(19) nucleophile and Mg(2+) cofactor. This suggests that substrate binds first to the cap and then is swept into the active site upon cap closure. The orientation of the acid/base residue Asp(21) suggests that alpha-phosphomannomutase (alpha-PMM) uses a different method of protecting the aspartylphosphate from hydrolysis than the HADSF member beta-phosphoglucomutase. It is hypothesized that the electrostatic repulsion of positive charges at the interface of the cap and core domains stabilizes alpha-PMM1 in the open conformation and that the negatively charged substrate binds to the cap, thereby facilitating its closure over the core domain. The two isozymes, alpha-PMM1 and alpha-PMM2, are shown to have a conserved active-site structure and to display similar kinetic properties. Analysis of the known mutation sites in the context of the structures reveals the genotype-phenotype relationship underlying CDG-1a."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m601505200"xsd:string
http://purl.uniprot.org/citations/16540464http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m601505200"xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Allen K.N."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Allen K.N."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Lu Z."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Lu Z."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Dunaway-Mariano D."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Dunaway-Mariano D."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Zhang C."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Zhang C."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Dai J."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Dai J."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Silvaggi N.R."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/author"Silvaggi N.R."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/pages"14918-14926"xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/pages"14918-14926"xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/title"The X-ray crystal structures of human alpha-phosphomannomutase 1 reveal the structural basis of congenital disorder of glycosylation type 1a."xsd:string
http://purl.uniprot.org/citations/16540464http://purl.uniprot.org/core/title"The X-ray crystal structures of human alpha-phosphomannomutase 1 reveal the structural basis of congenital disorder of glycosylation type 1a."xsd:string
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