5npb

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of cjAgd31B (alpha-transglucosylase from Glycoside Hydrolase Family 31) in complex with alpha Cyclophellitol Cyclosulfate probe ME647

Structural highlights

5npb is a 1 chain structure with sequence from Cellvibrio japonicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

OL4AG_CELJU Alpha-transglucosylase that specifically transfers single glucosyl units from alpha(1->4)-glucans to the non-reducing terminal 4-OH of glucose and alpha(1->4)- and alpha(1->6)-linked glucosyl residues. Acts on amylose, amylopectin, glycogen and maltooligosaccharides, with the highest activity with maltotriose as a donor, and also accepts maltose. Does not act as a hydrolase: weak hydrolysis activity is only observed on the disaccharide maltose.^[1]

Publication Abstract from PubMed

The essential biological roles played by glycosidases, coupled to the diverse therapeutic benefits of pharmacologically targeting these enzymes, provide considerable motivation for the development of new inhibitor classes. Cyclophellitol epoxides and aziridines are recently established covalent glycosidase inactivators. Inspired by the application of cyclic sulfates as electrophilic equivalents of epoxides in organic synthesis, we sought to test whether cyclophellitol cyclosulfates would similarly act as irreversible glycosidase inhibitors. Here we present the synthesis, conformational analysis, and application of novel 1,6-cyclophellitol cyclosulfates. We show that 1,6-epi-cyclophellitol cyclosulfate (alpha-cyclosulfate) is a rapidly reacting alpha-glucosidase inhibitor whose 4C1 chair conformation matches that adopted by alpha-glucosidase Michaelis complexes. The 1,6-cyclophellitol cyclosulfate (beta-cyclosulfate) reacts more slowly, likely reflecting its conformational restrictions. Selective glycosidase inhibitors are invaluable as mechanistic probes and therapeutic agents, and we propose cyclophellitol cyclosulfates as a valuable new class of carbohydrate mimetics for application in these directions.

1,6-Cyclophellitol Cyclosulfates: A New Class of Irreversible Glycosidase Inhibitor.,Artola M, Wu L, Ferraz MJ, Kuo CL, Raich L, Breen IZ, Offen WA, Codee JDC, van der Marel GA, Rovira C, Aerts JMFG, Davies GJ, Overkleeft HS ACS Cent Sci. 2017 Jul 26;3(7):784-793. doi: 10.1021/acscentsci.7b00214. Epub, 2017 Jul 13. PMID:28776021^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Larsbrink J, Izumi A, Hemsworth GR, Davies GJ, Brumer H. Structural enzymology of Cellvibrio japonicus Agd31B reveals alpha-transglucosylase activity in glycoside hydrolase family 31. J Biol Chem. 2012 Nov 6. PMID:23132856 doi:http://dx.doi.org/10.1074/jbc.M112.416511
↑ Artola M, Wu L, Ferraz MJ, Kuo CL, Raich L, Breen IZ, Offen WA, Codee JDC, van der Marel GA, Rovira C, Aerts JMFG, Davies GJ, Overkleeft HS. 1,6-Cyclophellitol Cyclosulfates: A New Class of Irreversible Glycosidase Inhibitor. ACS Cent Sci. 2017 Jul 26;3(7):784-793. doi: 10.1021/acscentsci.7b00214. Epub, 2017 Jul 13. PMID:28776021 doi:http://dx.doi.org/10.1021/acscentsci.7b00214

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5npb"

Categories: Cellvibrio japonicus | Large Structures | Davies GJ | Wu L

@@ Line 1: / Line 1: @@
 ==Crystal Structure of cjAgd31B (alpha-transglucosylase from Glycoside Hydrolase Family 31) in complex with alpha Cyclophellitol Cyclosulfate probe ME647==
-<StructureSection load='5npb' size='340' side='right' caption='[[5npb]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='5npb' size='340' side='right'caption='[[5npb]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5npb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NPB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NPB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5npb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cellvibrio_japonicus Cellvibrio japonicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NPB FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=93Z:[(1~{S},2~{R},3~{R},4~{S},5~{R})-2-(hydroxymethyl)-3,4,5,6-tetrakis(oxidanyl)cyclohexyl]+hydrogen+sulfate'>93Z</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Oligosaccharide_4-alpha-D-glucosyltransferase Oligosaccharide 4-alpha-D-glucosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.161 2.4.1.161] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=93Z:[(1~{S},2~{R},3~{R},4~{S},5~{R})-2-(hydroxymethyl)-3,4,5,6-tetrakis(oxidanyl)cyclohexyl]+hydrogen+sulfate'>93Z</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5npb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5npb OCA], [http://pdbe.org/5npb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5npb RCSB], [http://www.ebi.ac.uk/pdbsum/5npb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5npb ProSAT]</span></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=5npb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5npb OCA], [https://pdbe.org/5npb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5npb RCSB], [https://www.ebi.ac.uk/pdbsum/5npb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5npb ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/OL4AG_CELJU OL4AG_CELJU]] Alpha-transglucosylase that specifically transfers single glucosyl units from alpha(1->4)-glucans to the non-reducing terminal 4-OH of glucose and alpha(1->4)- and alpha(1->6)-linked glucosyl residues. Acts on amylose, amylopectin, glycogen and maltooligosaccharides, with the highest activity with maltotriose as a donor, and also accepts maltose. Does not act as a hydrolase: weak hydrolysis activity is only observed on the disaccharide maltose.<ref>PMID:23132856</ref>
+[https://www.uniprot.org/uniprot/OL4AG_CELJU OL4AG_CELJU] Alpha-transglucosylase that specifically transfers single glucosyl units from alpha(1->4)-glucans to the non-reducing terminal 4-OH of glucose and alpha(1->4)- and alpha(1->6)-linked glucosyl residues. Acts on amylose, amylopectin, glycogen and maltooligosaccharides, with the highest activity with maltotriose as a donor, and also accepts maltose. Does not act as a hydrolase: weak hydrolysis activity is only observed on the disaccharide maltose.<ref>PMID:23132856</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Oligosaccharide 4-alpha-D-glucosyltransferase]]
+[[Category: Cellvibrio japonicus]]
-[[Category: Davies, G J]]
+[[Category: Large Structures]]
-[[Category: Wu, L]]
+[[Category: Davies GJ]]
-[[Category: Hydrolase]]
+[[Category: Wu L]]

5npb

From Proteopedia

Current revision

Crystal Structure of cjAgd31B (alpha-transglucosylase from Glycoside Hydrolase Family 31) in complex with alpha Cyclophellitol Cyclosulfate probe ME647

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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