1h7n: Difference between revisions

Revision as of 18:32, 2 May 2008

SCHIFF-BASE COMPLEX OF YEAST 5-AMINOLAEVULINIC ACID DEHYDRATASE WITH LAEVULINIC ACID AT 1.6 A RESOLUTION

OverviewOverview

The structures of 5-aminolaevulinic acid dehydratase (ALAD) complexed with substrate (5-aminolaevulinic acid) and three inhibitors: laevulinic acid, succinylacetone and 4-keto-5-aminolaevulinic acid, have been solved at high resolution. The ligands all bind by forming a covalent link with Lys263 at the active site. The structures define the interactions made by one of the two substrate moieties that bind to the enzyme during catalysis. All of the inhibitors induce a significant ordering of the flap covering the active site. Succinylacetone appears to be unique by inducing a number of conformational changes in loops covering the active site, which may be important for understanding the co-operative properties of ALAD enzymes. Succinylacetone is produced in large amounts by patients suffering from the hereditary disease type I tyrosinaemia and its potent inhibition of ALAD also has implications for the pathology of this disease. The most intriguing result is that obtained with 4-keto-5-amino-hexanoic acid, which seems to form a stable carbinolamine intermediate with Lys263. It appears that we have defined the structure of an intermediate of Schiff base formation that the substrate forms upon binding to the P-site of the enzyme.

About this StructureAbout this Structure

1H7N is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

ReferenceReference

The x-ray structure of yeast 5-aminolaevulinic acid dehydratase complexed with substrate and three inhibitors., Erskine PT, Newbold R, Brindley AA, Wood SP, Shoolingin-Jordan PM, Warren MJ, Cooper JB, J Mol Biol. 2001 Sep 7;312(1):133-41. PMID:11545591 Page seeded by OCA on Fri May 2 18:32:25 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1h7n.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 1h7n |SIZE=350|CAPTION= <scene name='initialview01'>1h7n</scene>, resolution 1.6&Aring;
+The line below this paragraph, containing "STRUCTURE_1h7n", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Shf+Binding+Site+For+Chain+A'>AC1</scene> and <scene name='pdbsite=AC2:Zn+Binding+Site+For+Chain+A'>AC2</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=SHF:LAEVULINIC+ACID'>SHF</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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/Porphobilinogen_synthase Porphobilinogen synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.24 4.2.1.24] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1h7n|  PDB=1h7n  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h7n OCA], [http://www.ebi.ac.uk/pdbsum/1h7n PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1h7n RCSB]</span>
-}}
 '''SCHIFF-BASE COMPLEX OF YEAST 5-AMINOLAEVULINIC ACID DEHYDRATASE WITH LAEVULINIC ACID AT 1.6 A RESOLUTION'''
@@ Line 33: / Line 30: @@
 [[Category: Warren, M J.]]
 [[Category: Wood, S P.]]
-[[Category: aldolase]]
+[[Category: Aldolase]]
-[[Category: dehydratase]]
+[[Category: Dehydratase]]
-[[Category: lyase]]
+[[Category: Lyase]]
-[[Category: tetrapyrrole synthesis]]
+[[Category: Tetrapyrrole synthesis]]
-[[Category: tim barrel]]
+[[Category: Tim barrel]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 18:32:25 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:59:35 2008''