1w3j
From Proteopedia
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| - | [[Image:1w3j.gif|left|200px]]<br /> | + | [[Image:1w3j.gif|left|200px]]<br /><applet load="1w3j" size="450" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1w3j" size="450" color="white" frame="true" align="right" spinBox="true" | + | |
caption="1w3j, resolution 2.00Å" /> | caption="1w3j, resolution 2.00Å" /> | ||
'''FAMILY 1 B-GLUCOSIDASE FROM THERMOTOGA MARITIMA IN COMPLEX WITH TETRAHYDROOXAZINE'''<br /> | '''FAMILY 1 B-GLUCOSIDASE FROM THERMOTOGA MARITIMA IN COMPLEX WITH TETRAHYDROOXAZINE'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1W3J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with OXZ as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Beta-glucosidase Beta-glucosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.21 3.2.1.21] | + | 1W3J is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermotoga_maritima Thermotoga maritima] with OXZ as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Beta-glucosidase Beta-glucosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.21 3.2.1.21] Known structural/functional Site: <scene name='pdbsite=NUC:Oxz Binding Site For Chain A'>NUC</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W3J OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tetrahydrooxazine]] | [[Category: tetrahydrooxazine]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 18:28:56 2007'' |
Revision as of 16:19, 18 December 2007
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FAMILY 1 B-GLUCOSIDASE FROM THERMOTOGA MARITIMA IN COMPLEX WITH 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
1W3J is a Single protein structure of sequence from Thermotoga maritima with OXZ as ligand. Active as Beta-glucosidase, with EC number 3.2.1.21 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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