1u33
From Proteopedia
(New page: 200px<br /> <applet load="1u33" size="450" color="white" frame="true" align="right" spinBox="true" caption="1u33, resolution 1.95Å" /> '''In situ extension a...) |
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| - | [[Image:1u33.gif|left|200px]]<br /> | + | [[Image:1u33.gif|left|200px]]<br /><applet load="1u33" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1u33" size=" | + | |
caption="1u33, resolution 1.95Å" /> | caption="1u33, resolution 1.95Å" /> | ||
'''In situ extension as an approach for identifying novel alpha-amylase inhibitors'''<br /> | '''In situ extension as an approach for identifying novel alpha-amylase inhibitors'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A new approach for the discovery and subsequent structural elucidation of | + | 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 Structure== | ==About this Structure== | ||
| - | 1U33 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG, LM2, CA and CL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1U33 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene>, <scene name='pdbligand=LM2:'>LM2</scene>, <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=CL:'>CL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U33 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Begum, A.]] | [[Category: Begum, A.]] | ||
| - | [[Category: Brayer, G | + | [[Category: Brayer, G D.]] |
[[Category: Damager, I.]] | [[Category: Damager, I.]] | ||
[[Category: Li, C.]] | [[Category: Li, C.]] | ||
[[Category: Numao, S.]] | [[Category: Numao, S.]] | ||
| - | [[Category: Overall, C | + | [[Category: Overall, C M.]] |
| - | [[Category: Withers, S | + | [[Category: Withers, S G.]] |
| - | [[Category: Wrodnigg, T | + | [[Category: Wrodnigg, T M.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: inhibitor]] | [[Category: inhibitor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:20:05 2008'' |
Revision as of 13:20, 21 February 2008
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In situ extension as an approach for identifying novel alpha-amylase inhibitors
Overview
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 Structure
1U33 is a Single protein structure of sequence from Homo sapiens with , , and as ligands. Active as Alpha-amylase, with EC number 3.2.1.1 Full crystallographic information is available from OCA.
Reference
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 Thu Feb 21 15:20:05 2008
Categories: Alpha-amylase | Homo sapiens | Single protein | Begum, A. | Brayer, G D. | Damager, I. | Li, C. | Numao, S. | Overall, C M. | Withers, S G. | Wrodnigg, T M. | CA | CL | LM2 | NAG | Acarbose | Enzyme mechanism | Glucosidase | Glycosidase | Human pancreatic alpha-amylase | Inhibitor
