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1jak

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[[Image:1jak.gif|left|200px]]
[[Image:1jak.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1jak |SIZE=350|CAPTION= <scene name='initialview01'>1jak</scene>, resolution 1.75&Aring;
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The line below this paragraph, containing "STRUCTURE_1jak", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IFG:(2R,3R,4S,5R)-2-ACETAMIDO-3,4-DIHYDROXY-5-HYDROXYMETHYL-PIPERIDINE'>IFG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.52 3.2.1.52] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_1jak| PDB=1jak | SCENE= }}
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|RELATEDENTRY=[[1hp4|1HP4]], [[1hp5|1HP5]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1jak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jak OCA], [http://www.ebi.ac.uk/pdbsum/1jak PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1jak RCSB]</span>
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}}
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'''Streptomyces plicatus beta-N-acetylhexosaminidase in Complex with (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidinium chloride (IFG)'''
'''Streptomyces plicatus beta-N-acetylhexosaminidase in Complex with (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidinium chloride (IFG)'''
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[[Category: Withers, S G.]]
[[Category: Withers, S G.]]
[[Category: Zhao, D.]]
[[Category: Zhao, D.]]
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[[Category: alpha/beta barrel]]
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[[Category: Alpha/beta barrel]]
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[[Category: beta-n-acetylhexosaminidase]]
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[[Category: Beta-n-acetylhexosaminidase]]
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[[Category: family 20]]
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[[Category: Family 20]]
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[[Category: glycoside hydrolase]]
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[[Category: Glycoside hydrolase]]
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[[Category: isofagomine inhibitor complex]]
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[[Category: Isofagomine inhibitor complex]]
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[[Category: substrate-assisted catalysis]]
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[[Category: Substrate-assisted catalysis]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 20:59:02 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:30:48 2008''
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Revision as of 17:59, 2 May 2008

Image:1jak.gif

Template:STRUCTURE 1jak

Streptomyces plicatus beta-N-acetylhexosaminidase in Complex with (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidinium chloride (IFG)


Overview

Azasugar inhibitors of the isofagomine class are potent competitive inhibitors of configuration-retaining beta-glycosidases. This potency results from the formation of a strong electrostatic interaction between a protonated endocyclic nitrogen at the "anomeric" center of the inhibitor and the catalytic nucleophile of the enzyme. Although the majority of retaining beta-glycosidases use a mechanism involving a carboxylate residue as a nucleophile, Streptomyces plicatus beta-N-acetylhexos-aminidase (SpHEX) and related family 20 glycosidases lack such a catalytic residue and use instead the carbonyl oxygen of the 2-acetamido group of the substrate as a nucleophile to "attack" the anomeric center. Thus, a strong electrostatic interaction between the inhibitor and enzyme is not expected to occur; nonetheless, the 1-N-azasugar (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidinium hydrochloride (GalNAc-isofagomine.HCl), which was synthesized and assayed for its ability to inhibit SpHEX, was found to be a potent competitive inhibitor of the enzyme (K(i) = 2.7 microm). A crystallographic complex of GalNAc-isofagomine bound to SpHEX was solved and refined to 1.75 A and revealed that the lack of a strong electrostatic interaction between the "anomeric" center of GalNAc-isofagomine and SpHEX is compensated for by a novel 2.8-A hydrogen bond formed between the equatorial proton of the endocyclic nitrogen of the azasugar ring and the carboxylate of the general acid-base residue Glu-314 of SpHEX. This interaction appears to contribute to the unexpected potency of GalNAc-isofagomine toward SpHEX.

About this Structure

1JAK is a Single protein structure of sequence from Streptomyces plicatus. Full crystallographic information is available from OCA.

Reference

Biochemical and structural assessment of the 1-N-azasugar GalNAc-isofagomine as a potent family 20 beta-N-acetylhexosaminidase inhibitor., Mark BL, Vocadlo DJ, Zhao D, Knapp S, Withers SG, James MN, J Biol Chem. 2001 Nov 9;276(45):42131-7. Epub 2001 Aug 24. PMID:11522797 Page seeded by OCA on Fri May 2 20:59:02 2008

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