2fuc: Difference between revisions
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[[Image:2fuc.gif|left|200px]] | [[Image:2fuc.gif|left|200px]] | ||
'''Human alpha-Phosphomannomutase 1 with Mg2+ cofactor bound''' | {{Structure | ||
|PDB= 2fuc |SIZE=350|CAPTION= <scene name='initialview01'>2fuc</scene>, resolution 2.10Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM ION'>MG</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Phosphomannomutase Phosphomannomutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.4.2.8 5.4.2.8] | |||
|GENE= | |||
}} | |||
'''Human alpha-Phosphomannomutase 1 with Mg2+ cofactor bound''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2FUC is a [ | 2FUC is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FUC OCA]. | ||
==Reference== | ==Reference== | ||
The X-ray crystal structures of human alpha-phosphomannomutase 1 reveal the structural basis of congenital disorder of glycosylation type 1a., Silvaggi NR, Zhang C, Lu Z, Dai J, Dunaway-Mariano D, Allen KN, J Biol Chem. 2006 May 26;281(21):14918-26. Epub 2006 Mar 15. PMID:[http:// | The X-ray crystal structures of human alpha-phosphomannomutase 1 reveal the structural basis of congenital disorder of glycosylation type 1a., Silvaggi NR, Zhang C, Lu Z, Dai J, Dunaway-Mariano D, Allen KN, J Biol Chem. 2006 May 26;281(21):14918-26. Epub 2006 Mar 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16540464 16540464] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Phosphomannomutase]] | [[Category: Phosphomannomutase]] | ||
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[[Category: protein glycosylation]] | [[Category: protein glycosylation]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:56:50 2008'' | ||
Revision as of 17:56, 20 March 2008
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| , resolution 2.10Å | |||||||
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| Ligands: | |||||||
| Activity: | Phosphomannomutase, with EC number 5.4.2.8 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human alpha-Phosphomannomutase 1 with Mg2+ cofactor bound
OverviewOverview
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.
About this StructureAbout this Structure
2FUC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
The X-ray crystal structures of human alpha-phosphomannomutase 1 reveal the structural basis of congenital disorder of glycosylation type 1a., Silvaggi NR, Zhang C, Lu Z, Dai J, Dunaway-Mariano D, Allen KN, J Biol Chem. 2006 May 26;281(21):14918-26. Epub 2006 Mar 15. PMID:16540464
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