From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:2uu7.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:2uu7.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_2uu7| PDB=2uu7 | SCENE= }} | | {{STRUCTURE_2uu7| PDB=2uu7 | SCENE= }} |
| | | | |
| - | '''CRYSTAL STRUCTURE OF APO GLUTAMINE SYNTHETASE FROM DOG (CANIS FAMILIARIS)'''
| + | ===CRYSTAL STRUCTURE OF APO GLUTAMINE SYNTHETASE FROM DOG (CANIS FAMILIARIS)=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Glutamine synthetase (GS) catalyzes the ligation of glutamate and ammonia to form glutamine, with concomitant hydrolysis of ATP. In mammals, the activity eliminates cytotoxic ammonia, at the same time converting neurotoxic glutamate to harmless glutamine; there are a number of links between changes in GS activity and neurodegenerative disorders, such as Alzheimer's disease. In plants, because of its importance in the assimilation and re-assimilation of ammonia, the enzyme is a target of some herbicides. GS is also a central component of bacterial nitrogen metabolism and a potential drug target. Previous studies had investigated the structures of bacterial and plant GSs. In the present publication, we report the first structures of mammalian GSs. The apo form of the canine enzyme was solved by molecular replacement and refined at a resolution of 3 A. Two structures of human glutamine synthetase represent complexes with: a) phosphate, ADP, and manganese, and b) a phosphorylated form of the inhibitor methionine sulfoximine, ADP and manganese; these structures were refined to resolutions of 2.05 A and 2.6 A, respectively. Loop movements near the active site generate more closed forms of the eukaryotic enzymes when substrates are bound; the largest changes are associated with the binding of the nucleotide. Comparisons with earlier structures provide a basis for the design of drugs that are specifically directed at either human or bacterial enzymes. The site of binding the amino acid substrate is highly conserved in bacterial and eukaryotic GSs, whereas the nucleotide binding site varies to a much larger degree. Thus, the latter site offers the best target for specific drug design. Differences between mammalian and plant enzymes are much more subtle, suggesting that herbicides targeting GS must be designed with caution.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_18005987}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 18005987 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_18005987}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 27: |
Line 31: |
| | [[Category: Mowbray, S L.]] | | [[Category: Mowbray, S L.]] |
| | [[Category: Ligase]] | | [[Category: Ligase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:29:03 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 15:39:15 2008'' |
Revision as of 12:39, 28 July 2008
Template:STRUCTURE 2uu7
CRYSTAL STRUCTURE OF APO GLUTAMINE SYNTHETASE FROM DOG (CANIS FAMILIARIS)
Template:ABSTRACT PUBMED 18005987
About this Structure
2UU7 is a Single protein structure of sequence from Canis lupus familiaris. Full crystallographic information is available from OCA.
Reference
Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design., Krajewski WW, Collins R, Holmberg-Schiavone L, Jones TA, Karlberg T, Mowbray SL, J Mol Biol. 2008 Jan 4;375(1):217-28. Epub 2007 Oct 17. PMID:18005987
Page seeded by OCA on Mon Jul 28 15:39:15 2008
