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[[Image:1jak.gif|left|200px]]
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{{STRUCTURE_1jak|  PDB=1jak  |  SCENE=  }}
'''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)==
<StructureSection load='1jak' size='340' side='right'caption='[[1jak]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1jak]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_plicatus Streptomyces plicatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JAK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JAK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jak FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jak OCA], [https://pdbe.org/1jak PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jak RCSB], [https://www.ebi.ac.uk/pdbsum/1jak PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jak ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O85361_STRPL O85361_STRPL]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ja/1jak_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1jak ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==Overview==
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<ref>PMID:11522797</ref>
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==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1JAK is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_plicatus Streptomyces plicatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JAK OCA].
</div>
<div class="pdbe-citations 1jak" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://www.ncbi.nlm.nih.gov/pubmed/11522797 11522797]
*[[Beta-Hexosaminidase|Beta-Hexosaminidase]]
[[Category: Beta-N-acetylhexosaminidase]]
*[[Beta-Hexosaminidase 3D structures|Beta-Hexosaminidase 3D structures]]
[[Category: Single protein]]
*[[Beta-N-acetylhexosaminidase 3D structures|Beta-N-acetylhexosaminidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Streptomyces plicatus]]
[[Category: Streptomyces plicatus]]
[[Category: James, M N.]]
[[Category: James MN]]
[[Category: Knapp, S.]]
[[Category: Knapp S]]
[[Category: Mark, B L.]]
[[Category: Mark BL]]
[[Category: Vocadlo, D J.]]
[[Category: Vocadlo DJ]]
[[Category: Withers, S G.]]
[[Category: Withers SG]]
[[Category: Zhao, D.]]
[[Category: Zhao D]]
[[Category: Alpha/beta barrel]]
[[Category: Beta-n-acetylhexosaminidase]]
[[Category: Family 20]]
[[Category: Glycoside hydrolase]]
[[Category: Isofagomine inhibitor complex]]
[[Category: Substrate-assisted catalysis]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 20:59:02 2008''
Retrieved from "https://proteopedia.org/1jak"