1w3k
From Proteopedia
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| - | [[Image:1w3k.gif|left|200px]]<br /><applet load="1w3k" size=" | + | [[Image:1w3k.gif|left|200px]]<br /><applet load="1w3k" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1w3k, resolution 1.20Å" /> | caption="1w3k, resolution 1.20Å" /> | ||
'''ENDOGLUCANASE CEL5A FROM BACILLUS AGARADHAERENS IN COMPLEX WITH CELLOBIO DERIVED-TETRAHYDROOXAZINE'''<br /> | '''ENDOGLUCANASE CEL5A FROM BACILLUS AGARADHAERENS IN COMPLEX WITH CELLOBIO DERIVED-TETRAHYDROOXAZINE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1W3K is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_agaradhaerens Bacillus agaradhaerens] with BGC, SO4, OXZ and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:So4 Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http:// | + | 1W3K is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_agaradhaerens Bacillus agaradhaerens] with <scene name='pdbligand=BGC:'>BGC</scene>, <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=OXZ:'>OXZ</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W3K OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tetrahydrooxazine]] | [[Category: tetrahydrooxazine]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:18:53 2008'' |
Revision as of 08:18, 3 February 2008
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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 with , , and as ligands. Active as Cellulase, with EC number 3.2.1.4 Known structural/functional Site: . 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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