1w3k
From Proteopedia
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|PDB= 1w3k |SIZE=350|CAPTION= <scene name='initialview01'>1w3k</scene>, resolution 1.20Å | |PDB= 1w3k |SIZE=350|CAPTION= <scene name='initialview01'>1w3k</scene>, resolution 1.20Å | ||
|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OXZ:TETRAHYDROOXAZINE'>OXZ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Cellulase Cellulase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.4 3.2.1.4] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Cellulase Cellulase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.4 3.2.1.4] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w3k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w3k OCA], [http://www.ebi.ac.uk/pdbsum/1w3k PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1w3k RCSB]</span> | ||
}} | }} | ||
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[[Category: Tarling, C A.]] | [[Category: Tarling, C A.]] | ||
[[Category: Withers, S W.]] | [[Category: Withers, S W.]] | ||
| - | [[Category: BGC]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: OXZ]] | ||
| - | [[Category: SO4]] | ||
[[Category: cellulose degradation]] | [[Category: cellulose degradation]] | ||
[[Category: endoglucanase]] | [[Category: endoglucanase]] | ||
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[[Category: tetrahydrooxazine]] | [[Category: tetrahydrooxazine]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:30:42 2008'' |
Revision as of 21:30, 30 March 2008
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| , resolution 1.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , , | ||||||
| Activity: | Cellulase, with EC number 3.2.1.4 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
ENDOGLUCANASE CEL5A FROM BACILLUS AGARADHAERENS IN COMPLEX WITH CELLOBIO DERIVED-TETRAHYDROOXAZINE
Overview
The understanding of transition state mimicry in glycoside hydrolysis is increasingly important both in the quest for novel specific therapeutic agents and for the deduction of enzyme function and mechanism. To aid comprehension, inhibitors can be characterized through kinetic, thermodynamic, and structural dissection to build an "inhibition profile." Here we dissect the binding of a tetrahydrooxazine inhibitor and its derivatives, which display Ki values around 500 nm. X-ray structures with both a beta-glucosidase, at 2 A resolution, and an endoglucanase at atomic (approximately 1 A) resolution reveal similar interactions between the tetrahydrooxazine inhibitor and both enzymes. Kinetic analyses reveal the pH dependence of kcat/Km and 1/Ki with both enzyme systems, and isothermal titration calorimetry unveils the enthalpic and entropic contributions to beta-glucosidase inhibition. The pH dependence of enzyme activity mirrored that of 1/Ki in both enzymes, unlike the cases of isofagomine and 1-deoxynojirimycin that have been characterized previously. Calorimetric dissection reveals a large favorable enthalpy that is partially offset by an unfavorable entropy upon binding. In terms of the similar profile for the pH dependence of 1/Ki and the pH dependence of kcat/Km, the significant enthalpy of binding when compared with other glycosidase inhibitors, and the tight binding at the optimal pH of the enzymes tested, tetrahydrooxazine and its derivatives are a significantly better class of glycosidase inhibitor than previously assumed.
About this Structure
1W3K is a Single protein structure of sequence from Bacillus agaradhaerens. Full crystallographic information is available from OCA.
Reference
Structural, thermodynamic, and kinetic analyses of tetrahydrooxazine-derived inhibitors bound to beta-glucosidases., Gloster TM, Macdonald JM, Tarling CA, Stick RV, Withers SG, Davies GJ, J Biol Chem. 2004 Nov 19;279(47):49236-42. Epub 2004 Sep 8. PMID:15356002
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