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| - | [[Image:2fyv.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2fyv| PDB=2fyv | SCENE= }} | | {{STRUCTURE_2fyv| PDB=2fyv | SCENE= }} |
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| - | '''Golgi alpha-mannosidase II complex with an amino-salacinol carboxylate analog'''
| + | ===Golgi alpha-mannosidase II complex with an amino-salacinol carboxylate analog=== |
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| - | ==Overview==
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| - | The synthesis of two novel amino acids, nitrogen analogues of the naturally occurring glycosidase inhibitor, salacinol, containing a carboxylate inner salt are described, along with the crystal structure of one of these analogues in the active site of Drosophila melanogaster Golgi mannosidase II (dGMII). Salacinol, a naturally occurring sulfonium ion, is one of the active principals in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The synthetic strategy relies on the nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-imino l- or d-arabinitol at the least hindered carbon of 5,6-anhydro-2,3-di-O-benzyl-l-ascorbic acid to yield coupled adducts. Deprotection, stereoselective catalytic reduction, and hydrolysis of the coupled products give the target compounds. The compound derived from d-arabinitol inhibits dGMII, one of the critical enzymes in the glycoprotein processing pathway, with an IC(50) of 0.3mM. Inhibition of GMII has been identified as a target for control of metastatic cancer. An X-ray crystal structure of the complex of this compound with dGMII provides insight into the requirements for an effective inhibitor. The same compound inhibits recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with a K(i) value of 21microM. | + | The line below this paragraph, {{ABSTRACT_PUBMED_17010621}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17010621 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17010621}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Rose, D R.]] | | [[Category: Rose, D R.]] |
| | [[Category: Glycosyl hydrolase family 38]] | | [[Category: Glycosyl hydrolase family 38]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:28:01 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 17:47:18 2008'' |
Revision as of 14:47, 27 July 2008
Template:STRUCTURE 2fyv
Golgi alpha-mannosidase II complex with an amino-salacinol carboxylate analog
Template:ABSTRACT PUBMED 17010621
About this Structure
2FYV is a Single protein structure of sequence from Drosophila melanogaster. Full crystallographic information is available from OCA.
Reference
Synthesis, enzymatic activity, and X-ray crystallography of an unusual class of amino acids., Chen W, Kuntz DA, Hamlet T, Sim L, Rose DR, Mario Pinto B, Bioorg Med Chem. 2006 Dec 15;14(24):8332-40. Epub 2006 Sep 28. PMID:17010621
Page seeded by OCA on Sun Jul 27 17:47:18 2008
