2qa3: Difference between revisions

Revision as of 14:36, 4 May 2008

Structural Studies Reveal the Inactivation of E. coli L-aspartate aminotransferase by (S)-4,5-amino-dihydro-2-thiophenecarboxylic acid (SADTA) via two mechanisms (at pH6.5)

OverviewOverview

As a mechanism-based inactivator of PLP-enzymes, (S)-4-amino-4,5-dihydro-2-thiophenecarboxylic acid (SADTA) was cocrystallized with Escherichia coli aspartate aminotransferase (l-AspAT) at a series of pH values ranging from 6 to 8. Five structural models with high resolution (1.4-1.85 A) were obtained for l-AspAT-SADTA complexes at pH 6.0, 6.5, 7.0, 7.5, and 8.0. Electron densities of the models showed that two different adducts had formed in the active sites. One adduct was formed from SADTA covalently linked to pyridoxal 5'-phosphate (PLP) while the other adduct was formed with the inhibitor covalently linked to Lysine246,1 the active site lysine. Moreover, there is a strong indication based on the electron densities that the occurrence of the two adducts is pH dependent. We conclude that SADTA inactivates l-AspAT via two different mechanisms based on the binding direction of the inactivator. Additionally, the structural models also show pH dependence of the protein structure itself, which provided detailed mechanistic implications for l-AspAT.

About this StructureAbout this Structure

2QA3 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

ReferenceReference

Inactivation of Escherichia coli L-aspartate aminotransferase by (S)-4-amino-4,5-dihydro-2-thiophenecarboxylic acid reveals "a tale of two mechanisms"., Liu D, Pozharski E, Lepore BW, Fu M, Silverman RB, Petsko GA, Ringe D, Biochemistry. 2007 Sep 18;46(37):10517-27. Epub 2007 Aug 22. PMID:17713924 Page seeded by OCA on Sun May 4 14:36:46 2008

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OCA

@@ Line 1: / Line 1: @@
 [[Image:2qa3.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2qa3 |SIZE=350|CAPTION= <scene name='initialview01'>2qa3</scene>, resolution 1.75&Aring;
+The line below this paragraph, containing "STRUCTURE_2qa3", 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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KST:N~6~-(5-CARBOXY-3-THIENYL)-L-LYSINE'>KST</scene>, <scene name='pdbligand=PMP:4&#39;-DEOXY-4&#39;-AMINOPYRIDOXAL-5&#39;-PHOSPHATE'>PMP</scene>, <scene name='pdbligand=PSZ:4-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]THIOPHENE-2-CARBOXYLIC+ACID'>PSZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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/Aspartate_transaminase Aspartate transaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.6.1.1 2.6.1.1] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= aspC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])
+-->
-|DOMAIN=
+{{STRUCTURE_2qa3|  PDB=2qa3  |  SCENE=  }}
-|RELATEDENTRY=[[2q7w|2Q7W]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qa3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qa3 OCA], [http://www.ebi.ac.uk/pdbsum/2qa3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qa3 RCSB]</span>
-}}
 '''Structural Studies Reveal the Inactivation of E. coli L-aspartate aminotransferase by (S)-4,5-amino-dihydro-2-thiophenecarboxylic acid (SADTA) via two mechanisms (at pH6.5)'''
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 [[Category: Ringe, D.]]
 [[Category: Silverman, R B.]]
-[[Category: asparate aminotransferase]]
+[[Category: Asparate aminotransferase]]
-[[Category: e. coli]]
+[[Category: E. coli]]
-[[Category: mechanism-based inhibitor]]
+[[Category: Mechanism-based inhibitor]]
-[[Category: plp]]
+[[Category: Plp]]
-[[Category: sadta]]
+[[Category: Sadta]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 14:36:46 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:46:48 2008''