2puw: Difference between revisions

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The crystal structure of isomerase domain of glucosamine-6-phosphate synthase from Candida albicans

OverviewOverview

Glucosamine 6-phosphate (GlcN-6-P) synthase is an ubiquitous enzyme that catalyses the first committed step in the reaction pathway that leads to formation of uridine 5'-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc), a precursor of macromolecules that contain amino sugars. Despite sequence similarities, the enzyme in eukaryotes is tetrameric, whereas in prokaryotes it is a dimer. The activity of eukaryotic GlcN-6-P synthase (known as Gfa1p) is regulated by feedback inhibition by UDP-GlcNAc, the end product of the reaction pathway, whereas in prokaryotes the GlcN-6-P synthase (known as GlmS) is not regulated at the post-translational level. In bacteria and fungi the enzyme is essential for cell wall synthesis. In human the enzyme is a mediator of insulin resistance. For these reasons, Gfa1p is a target in anti-fungal chemotherapy and in therapeutics for type-2 diabetes. The crystal structure of the Gfa1p isomerase domain from Candida albicans has been analysed in complex with the allosteric inhibitor UDP-GlcNAc and in the presence of glucose 6-phosphate, fructose 6-phosphate and an analogue of the reaction intermediate, 2-amino-2-deoxy-d-mannitol 6-phosphate (ADMP). A solution structure of the native Gfa1p has been deduced using small-angle X-ray scattering (SAXS). The tetrameric Gfa1p can be described as a dimer of dimers, with each half similar to the related enzyme from Escherichia coli. The core of the protein consists of the isomerase domains. UDP-GlcNAc binds, together with a metal cation, in a well-defined pocket on the surface of the isomerase domain. The residues responsible for tetramerisation and for binding UDP-GlcNAc are conserved only among eukaryotic sequences. Comparison with the previously studied GlmS from E. coli reveals differences as well as similarities in the isomerase active site. This study of Gfa1p focuses on the features that distinguish it from the prokaryotic homologue in terms of quaternary structure, control of the enzymatic activity and details of the isomerase active site.

About this StructureAbout this Structure

2PUW is a Single protein structure of sequence from Candida albicans. Full crystallographic information is available from OCA.

ReferenceReference

The crystal and solution studies of glucosamine-6-phosphate synthase from Candida albicans., Raczynska J, Olchowy J, Konariev PV, Svergun DI, Milewski S, Rypniewski W, J Mol Biol. 2007 Sep 21;372(3):672-88. Epub 2007 Jul 12. PMID:17681543 Page seeded by OCA on Sun May 4 13:50:27 2008

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OCA

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 [[Image:2puw.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2puw |SIZE=350|CAPTION= <scene name='initialview01'>2puw</scene>, resolution 3.151&Aring;
+The line below this paragraph, containing "STRUCTURE_2puw", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=BG6:BETA-D-GLUCOSE-6-PHOSPHATE'>BG6</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutamine--fructose-6-phosphate_transaminase_(isomerizing) Glutamine--fructose-6-phosphate transaminase (isomerizing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.16 2.6.1.16] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= GFA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5476 Candida albicans])
+-->
-|DOMAIN=
+{{STRUCTURE_2puw|  PDB=2puw  |  SCENE=  }}
-|RELATEDENTRY=[[2poc|2POC]], [[2put|2PUT]], [[2puv|2PUV]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2puw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2puw OCA], [http://www.ebi.ac.uk/pdbsum/2puw PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2puw RCSB]</span>
-}}
 '''The crystal structure of isomerase domain of glucosamine-6-phosphate synthase from Candida albicans'''
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 The crystal and solution studies of glucosamine-6-phosphate synthase from Candida albicans., Raczynska J, Olchowy J, Konariev PV, Svergun DI, Milewski S, Rypniewski W, J Mol Biol. 2007 Sep 21;372(3):672-88. Epub 2007 Jul 12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17681543 17681543]
 [[Category: Candida albicans]]
-[[Category: Glutamine--fructose-6-phosphate transaminase (isomerizing)]]
 [[Category: Single protein]]
 [[Category: Milewski, S.]]
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 [[Category: Raczynska, J.]]
 [[Category: Rypniewski, W.]]
-[[Category: aldose/ketose isomerase]]
+[[Category: Aldose/ketose isomerase]]
-[[Category: crystal structure]]
+[[Category: Crystal structure]]
-[[Category: glucosamine-6-phosphate synthase]]
+[[Category: Glucosamine-6-phosphate synthase]]
-[[Category: rossmann-like fold;]]
+[[Category: Rossmann-like fold;]]
-[[Category: transferase]]
+[[Category: Transferase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 13:50:27 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:41:02 2008''