2vjx

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(New page: 200px {{Structure |PDB= 2vjx |SIZE=350|CAPTION= <scene name='initialview01'>2vjx</scene>, resolution 1.85&Aring; |SITE= <scene name='pdbsite=AC1:Ifl+Binding+Site+...)
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{{Structure
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|PDB= 2vjx |SIZE=350|CAPTION= <scene name='initialview01'>2vjx</scene>, resolution 1.85&Aring;
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The line below this paragraph, containing "STRUCTURE_2vjx", creates the "Structure Box" on the page.
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IFL:(3S,4R,5R)-3,4-DIHYDROXY-5-(HYDROXYMETHYL)PIPERIDIN-2-ONE'>IFL</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-mannosidase Beta-mannosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.25 3.2.1.25] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam02837 Glyco_hydro_2_N], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=COG3250 LacZ], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam02836 Glyco_hydro_2_C]</span>
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{{STRUCTURE_2vjx| PDB=2vjx | SCENE= }}
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|RELATEDENTRY=[[2vqt|2VQT]], [[2vot|2VOT]], [[2vl4|2VL4]], [[2vqu|2VQU]], [[2vo5|2VO5]], [[2je8|2JE8]], [[2vjx|2VJX]], [[2vmf|2VMF]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vjx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vjx OCA], [http://www.ebi.ac.uk/pdbsum/2vjx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2vjx RCSB]</span>
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}}
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'''STRUCTURAL AND BIOCHEMICAL EVIDENCE FOR A BOAT-LIKE TRANSITION STATE IN BETA-MANNOSIDASES'''
'''STRUCTURAL AND BIOCHEMICAL EVIDENCE FOR A BOAT-LIKE TRANSITION STATE IN BETA-MANNOSIDASES'''
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==Overview==
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Enzyme inhibition through mimicry of the transition state is a major area for the design of new therapeutic agents. Emerging evidence suggests that many retaining glycosidases that are active on alpha- or beta-mannosides harness unusual B2,5 (boat) transition states. Here we present the analysis of 25 putative beta-mannosidase inhibitors, whose Ki values range from nanomolar to millimolar, on the Bacteroides thetaiotaomicron beta-mannosidase BtMan2A. B2,5 or closely related conformations were observed for all tightly binding compounds. Subsequent linear free energy relationships that correlate log Ki with log Km/kcat for a series of active center variants highlight aryl-substituted mannoimidazoles as powerful transition state mimics in which the binding energy of the aryl group enhances both binding and the degree of transition state mimicry. Support for a B2,5 transition state during enzymatic beta-mannosidase hydrolysis should also facilitate the design and exploitation of transition state mimics for the inhibition of retaining alpha-mannosidases--an area that is emerging for anticancer therapeutics.
==About this Structure==
==About this Structure==
2VJX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron Bacteroides thetaiotaomicron]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VJX OCA].
2VJX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron Bacteroides thetaiotaomicron]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VJX OCA].
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==Reference==
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Structural and biochemical evidence for a boat-like transition state in beta-mannosidases., Tailford LE, Offen WA, Smith NL, Dumon C, Morland C, Gratien J, Heck MP, Stick RV, Bleriot Y, Vasella A, Gilbert HJ, Davies GJ, Nat Chem Biol. 2008 May;4(5):306-12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18408714 18408714]
[[Category: Bacteroides thetaiotaomicron]]
[[Category: Bacteroides thetaiotaomicron]]
[[Category: Beta-mannosidase]]
[[Category: Beta-mannosidase]]
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[[Category: Moreland, C.]]
[[Category: Moreland, C.]]
[[Category: Offen, W A.]]
[[Category: Offen, W A.]]
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[[Category: Smith, N.]]
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[[Category: Smith, N L.]]
[[Category: Stick, R V.]]
[[Category: Stick, R V.]]
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[[Category: Tailford, L N.]]
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[[Category: Tailford, L E.]]
[[Category: Vasella, A.]]
[[Category: Vasella, A.]]
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[[Category: glycoside hydrolase]]
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[[Category: Glycoside hydrolase]]
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[[Category: hydrolase]]
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[[Category: Hydrolase]]
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[[Category: linear free energy relationship]]
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[[Category: Linear free energy relationship]]
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[[Category: mannosidase]]
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[[Category: Mannosidase]]
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[[Category: transition state mimic]]
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[[Category: Transition state mimic]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 24 09:30:24 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 2 11:58:36 2008''
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Revision as of 06:30, 24 April 2008

Image:2vjx.jpg

Template:STRUCTURE 2vjx

STRUCTURAL AND BIOCHEMICAL EVIDENCE FOR A BOAT-LIKE TRANSITION STATE IN BETA-MANNOSIDASES


Overview

Enzyme inhibition through mimicry of the transition state is a major area for the design of new therapeutic agents. Emerging evidence suggests that many retaining glycosidases that are active on alpha- or beta-mannosides harness unusual B2,5 (boat) transition states. Here we present the analysis of 25 putative beta-mannosidase inhibitors, whose Ki values range from nanomolar to millimolar, on the Bacteroides thetaiotaomicron beta-mannosidase BtMan2A. B2,5 or closely related conformations were observed for all tightly binding compounds. Subsequent linear free energy relationships that correlate log Ki with log Km/kcat for a series of active center variants highlight aryl-substituted mannoimidazoles as powerful transition state mimics in which the binding energy of the aryl group enhances both binding and the degree of transition state mimicry. Support for a B2,5 transition state during enzymatic beta-mannosidase hydrolysis should also facilitate the design and exploitation of transition state mimics for the inhibition of retaining alpha-mannosidases--an area that is emerging for anticancer therapeutics.

About this Structure

2VJX is a Single protein structure of sequence from Bacteroides thetaiotaomicron. Full crystallographic information is available from OCA.

Reference

Structural and biochemical evidence for a boat-like transition state in beta-mannosidases., Tailford LE, Offen WA, Smith NL, Dumon C, Morland C, Gratien J, Heck MP, Stick RV, Bleriot Y, Vasella A, Gilbert HJ, Davies GJ, Nat Chem Biol. 2008 May;4(5):306-12. PMID:18408714 Page seeded by OCA on Thu Apr 24 09:30:24 2008

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