1u30: Difference between revisions

Revision as of 10:41, 3 May 2008

In situ extension as an approach for identifying novel alpha-amylase inhibitors, structure containing maltosyl-alpha (1,4)-D-gluconhydroximo-1,5-lactam

OverviewOverview

A new approach for the discovery and subsequent structural elucidation of oligosaccharide-based inhibitors of alpha-amylases based upon autoglucosylation of known alpha-glucosidase inhibitors is presented. This concept, highly analogous to what is hypothesized to occur with acarbose, is demonstrated with the known alpha-glucosidase inhibitor, d-gluconohydroximino-1,5-lactam. This was transformed from an inhibitor of human pancreatic alpha-amylase with a K(i) value of 18 mm to a trisaccharide analogue with a K(i) value of 25 mum. The three-dimensional structure of this complex was determined by x-ray crystallography and represents the first such structure determined with this class of inhibitors in any alpha-glycosidase. This approach to the discovery and structural analysis of amylase inhibitors should be generally applicable to other endoglucosidases and readily adaptable to a high throughput format.

About this StructureAbout this Structure

1U30 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

In situ extension as an approach for identifying novel alpha-amylase inhibitors., Numao S, Damager I, Li C, Wrodnigg TM, Begum A, Overall CM, Brayer GD, Withers SG, J Biol Chem. 2004 Nov 12;279(46):48282-91. Epub 2004 Aug 10. PMID:15304511 Page seeded by OCA on Sat May 3 10:41:40 2008

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

OCA

@@ Line 1: / Line 1: @@
 [[Image:1u30.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1u30 |SIZE=350|CAPTION= <scene name='initialview01'>1u30</scene>, resolution 1.90&Aring;
+The line below this paragraph, containing "STRUCTURE_1u30", 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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOX:(2S,3S,4R,5R)-6-(HYDROXYAMINO)-2-(HYDROXYMETHYL)-2,3,4,5-TETRAHYDROPYRIDINE-3,4,5-TRIOL'>GOX</scene>, <scene name='pdbligand=LAG:MALTOSYL-ALPHA+(1,4)-(Z,3S,4S,5R,6R)-3,4,5-TRIHYDROXY-6-HYDROXYMETHYL-PIPERIDIN-2-ONE+OXIME'>LAG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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/Alpha-amylase Alpha-amylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.1 3.2.1.1] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= AMY2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_1u30|  PDB=1u30  |  SCENE=  }}
-|RELATEDENTRY=[[1u2y|1U2Y]], [[1u33|1U33]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u30 OCA], [http://www.ebi.ac.uk/pdbsum/1u30 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1u30 RCSB]</span>
-}}
 '''In situ extension as an approach for identifying novel alpha-amylase inhibitors, structure containing maltosyl-alpha (1,4)-D-gluconhydroximo-1,5-lactam'''
@@ Line 34: / Line 31: @@
 [[Category: Withers, S G.]]
 [[Category: Wrodnigg, T M.]]
-[[Category: acarbose]]
+[[Category: Acarbose]]
-[[Category: enzyme mechanism]]
+[[Category: Enzyme mechanism]]
-[[Category: glucosidase]]
+[[Category: Glucosidase]]
-[[Category: glycosidase]]
+[[Category: Glycosidase]]
-[[Category: human pancreatic alpha-amylase]]
+[[Category: Human pancreatic alpha-amylase]]
-[[Category: inhibitor]]
+[[Category: Inhibitor]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 10:41:40 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:04:43 2008''