2fuc
From Proteopedia
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|PDB= 2fuc |SIZE=350|CAPTION= <scene name='initialview01'>2fuc</scene>, resolution 2.10Å | |PDB= 2fuc |SIZE=350|CAPTION= <scene name='initialview01'>2fuc</scene>, resolution 2.10Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM ION'>MG</scene> | + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2fue|2FUE]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fuc OCA], [http://www.ebi.ac.uk/pdbsum/2fuc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fuc RCSB]</span> | ||
}} | }} | ||
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[[Category: Silvaggi, N R.]] | [[Category: Silvaggi, N R.]] | ||
[[Category: Zhang, C.]] | [[Category: Zhang, C.]] | ||
| - | [[Category: MG]] | ||
[[Category: carbohydrate-deficient glycoprotein syndrome]] | [[Category: carbohydrate-deficient glycoprotein syndrome]] | ||
[[Category: haloalkanoic acid dehalogenase superfamily]] | [[Category: haloalkanoic acid dehalogenase superfamily]] | ||
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[[Category: protein glycosylation]] | [[Category: protein glycosylation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:07:45 2008'' |
Revision as of 00:07, 31 March 2008
| |||||||
| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Activity: | Phosphomannomutase, with EC number 5.4.2.8 | ||||||
| Related: | 2FUE
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human alpha-Phosphomannomutase 1 with Mg2+ cofactor bound
Overview
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 Structure
2FUC is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
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:16540464
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