2vmf: Difference between revisions

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New page: left|200px {{Structure |PDB= 2vmf |SIZE=350|CAPTION= <scene name='initialview01'>2vmf</scene>, resolution 2.10Å |SITE= <scene name='pdbsite=AC1:Mvl+Binding+Site+...
 
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[[Image:2vmf.jpg|left|200px]]


{{Structure
==Structural and biochemical evidence for a boat-like transition state in beta-mannosidases==
|PDB= 2vmf |SIZE=350|CAPTION= <scene name='initialview01'>2vmf</scene>, resolution 2.10&Aring;
<StructureSection load='2vmf' size='340' side='right'caption='[[2vmf]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
|SITE= <scene name='pdbsite=AC1:Mvl+Binding+Site+For+Residue+A+1865'>AC1</scene>, <scene name='pdbsite=AC2:Mvl+Binding+Site+For+Residue+A+1865'>AC2</scene>, <scene name='pdbsite=AC3:Edo+Binding+Site+For+Residue+A+1866'>AC3</scene>, <scene name='pdbsite=AC4:Edo+Binding+Site+For+Residue+A+1867'>AC4</scene>, <scene name='pdbsite=AC5:Edo+Binding+Site+For+Residue+A+1868'>AC5</scene>, <scene name='pdbsite=AC6:Edo+Binding+Site+For+Residue+A+1869'>AC6</scene>, <scene name='pdbsite=AC7:Edo+Binding+Site+For+Residue+A+1870'>AC7</scene>, <scene name='pdbsite=AC8:Edo+Binding+Site+For+Residue+A+1871'>AC8</scene>, <scene name='pdbsite=AC9:Edo+Binding+Site+For+Residue+A+1872'>AC9</scene>, <scene name='pdbsite=BC1:Edo+Binding+Site+For+Residue+A+1873'>BC1</scene>, <scene name='pdbsite=BC2:Edo+Binding+Site+For+Residue+A+1874'>BC2</scene>, <scene name='pdbsite=BC3:Edo+Binding+Site+For+Residue+A+1875'>BC3</scene>, <scene name='pdbsite=BC4:Edo+Binding+Site+For+Residue+A+1876'>BC4</scene>, <scene name='pdbsite=BC5:Edo+Binding+Site+For+Residue+A+1877'>BC5</scene>, <scene name='pdbsite=BC6:Edo+Binding+Site+For+Residue+A+1878'>BC6</scene>, <scene name='pdbsite=BC7:Edo+Binding+Site+For+Residue+A+1879'>BC7</scene>, <scene name='pdbsite=BC8:Edo+Binding+Site+For+Residue+A+1880'>BC8</scene>, <scene name='pdbsite=BC9:Br+Binding+Site+For+Residue+A+1881'>BC9</scene>, <scene name='pdbsite=CC1:Br+Binding+Site+For+Residue+A+1885'>CC1</scene>, <scene name='pdbsite=CC2:Cl+Binding+Site+For+Residue+A+1887'>CC2</scene>, <scene name='pdbsite=CC3:Edo+Binding+Site+For+Residue+A+1888'>CC3</scene>, <scene name='pdbsite=CC4:Br+Binding+Site+For+Residue+A+1889'>CC4</scene>, <scene name='pdbsite=CC5:Cl+Binding+Site+For+Residue+A+1891'>CC5</scene>, <scene name='pdbsite=CC6:Edo+Binding+Site+For+Residue+A+1892'>CC6</scene>, <scene name='pdbsite=CC7:Edo+Binding+Site+For+Residue+A+1893'>CC7</scene>, <scene name='pdbsite=CC8:Edo+Binding+Site+For+Residue+A+1895'>CC8</scene>, <scene name='pdbsite=CC9:Edo+Binding+Site+For+Residue+A+1896'>CC9</scene>, <scene name='pdbsite=DC1:Cl+Binding+Site+For+Residue+A+1897'>DC1</scene>, <scene name='pdbsite=DC2:Mvl+Binding+Site+For+Residue+B+1868'>DC2</scene>, <scene name='pdbsite=DC3:Mvl+Binding+Site+For+Residue+B+1868'>DC3</scene>, <scene name='pdbsite=DC4:Edo+Binding+Site+For+Residue+B+1869'>DC4</scene>, <scene name='pdbsite=DC5:Edo+Binding+Site+For+Residue+B+1870'>DC5</scene>, <scene name='pdbsite=DC6:Edo+Binding+Site+For+Residue+B+1871'>DC6</scene>, <scene name='pdbsite=DC7:Edo+Binding+Site+For+Residue+B+1872'>DC7</scene>, <scene name='pdbsite=DC8:Edo+Binding+Site+For+Residue+B+1873'>DC8</scene>, <scene name='pdbsite=DC9:Edo+Binding+Site+For+Residue+B+1874'>DC9</scene>, <scene name='pdbsite=EC1:Edo+Binding+Site+For+Residue+B+1875'>EC1</scene>, <scene name='pdbsite=EC2:Edo+Binding+Site+For+Residue+B+1876'>EC2</scene>, <scene name='pdbsite=EC3:Edo+Binding+Site+For+Residue+B+1877'>EC3</scene>, <scene name='pdbsite=EC4:Edo+Binding+Site+For+Residue+B+1878'>EC4</scene>, <scene name='pdbsite=EC5:Br+Binding+Site+For+Residue+B+1879'>EC5</scene>, <scene name='pdbsite=EC6:Br+Binding+Site+For+Residue+B+1880'>EC6</scene>, <scene name='pdbsite=EC7:Cl+Binding+Site+For+Residue+B+1883'>EC7</scene>, <scene name='pdbsite=EC8:Cl+Binding+Site+For+Residue+B+1884'>EC8</scene>, <scene name='pdbsite=EC9:Cl+Binding+Site+For+Residue+B+1886'>EC9</scene>, <scene name='pdbsite=FC1:Edo+Binding+Site+For+Residue+B+1888'>FC1</scene>, <scene name='pdbsite=FC2:Edo+Binding+Site+For+Residue+B+1889'>FC2</scene>, <scene name='pdbsite=FC3:Edo+Binding+Site+For+Residue+B+1890'>FC3</scene>, <scene name='pdbsite=FC4:Br+Binding+Site+For+Residue+B+1891'>FC4</scene>, <scene name='pdbsite=FC5:Cl+Binding+Site+For+Residue+B+1892'>FC5</scene>, <scene name='pdbsite=FC6:Cl+Binding+Site+For+Residue+B+1893'>FC6</scene>, <scene name='pdbsite=FC7:Edo+Binding+Site+For+Residue+B+1894'>FC7</scene>, <scene name='pdbsite=FC8:Br+Binding+Site+For+Residue+B+1901'>FC8</scene>, <scene name='pdbsite=FC9:Edo+Binding+Site+For+Residue+B+1895'>FC9</scene>, <scene name='pdbsite=GC1:Edo+Binding+Site+For+Residue+B+1896'>GC1</scene>, <scene name='pdbsite=GC2:Cl+Binding+Site+For+Residue+B+1897'>GC2</scene>, <scene name='pdbsite=GC3:Edo+Binding+Site+For+Residue+B+1898'>GC3</scene>, <scene name='pdbsite=GC4:Edo+Binding+Site+For+Residue+B+1899'>GC4</scene>, <scene name='pdbsite=GC5:Edo+Binding+Site+For+Residue+B+1900'>GC5</scene> and <scene name='pdbsite=GC6:Edo+Binding+Site+For+Residue+A+1899'>GC6</scene>
== Structural highlights ==
|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=MVL:(5R,6R,7S,8R)-6,7,8-TRIHYDROXY-5-(HYDROXYMETHYL)-5,6,7,8-TETRAHYDRO-1H-IMIDAZO[1,2-A]PYRIDIN-4-IUM'>MVL</scene>
<table><tr><td colspan='2'>[[2vmf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron_VPI-5482 Bacteroides thetaiotaomicron VPI-5482]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VMF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VMF FirstGlance]. <br>
|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>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
|GENE=
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=MVL:(5R,6R,7S,8R)-5-(HYDROXYMETHYL)-5,6,7,8-TETRAHYDROIMIDAZO[1,2-A]PYRIDINE-6,7,8-TRIOL'>MVL</scene></td></tr>
|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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vmf OCA], [https://pdbe.org/2vmf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vmf RCSB], [https://www.ebi.ac.uk/pdbsum/2vmf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vmf ProSAT]</span></td></tr>
|RELATEDENTRY=[[2vqt|2VQT]], [[2vot|2VOT]], [[2vl4|2VL4]], [[2vqu|2VQU]], [[2vo5|2VO5]], [[2je8|2JE8]], [[2vjx|2VJX]]
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vmf OCA], [http://www.ebi.ac.uk/pdbsum/2vmf PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2vmf RCSB]</span>
== Function ==
}}
[https://www.uniprot.org/uniprot/Q8AAK6_BACTN Q8AAK6_BACTN]  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vm/2vmf_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vmf ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


'''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.,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<ref>PMID:18408714</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2vmf" style="background-color:#fffaf0;"></div>


==About this Structure==
==See Also==
2VMF 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=2VMF OCA].
*[[Mannosidase 3D structures|Mannosidase 3D structures]]
[[Category: Bacteroides thetaiotaomicron]]
== References ==
[[Category: Beta-mannosidase]]
<references/>
[[Category: Single protein]]
__TOC__
[[Category: Bleriot, Y.]]
</StructureSection>
[[Category: Davies, G J.]]
[[Category: Bacteroides thetaiotaomicron VPI-5482]]
[[Category: Dumon, C.]]
[[Category: Large Structures]]
[[Category: Gilbert, H J.]]
[[Category: Bleriot Y]]
[[Category: Gratien, J.]]
[[Category: Davies GJ]]
[[Category: Heck, M P.]]
[[Category: Dumon C]]
[[Category: Moreland, C.]]
[[Category: Gilbert HJ]]
[[Category: Offen, W A.]]
[[Category: Gratien J]]
[[Category: Smith, N.]]
[[Category: Heck MP]]
[[Category: Stick, R V.]]
[[Category: Moreland C]]
[[Category: Tailford, L N.]]
[[Category: Offen WA]]
[[Category: Vasella, A.]]
[[Category: Smith NL]]
[[Category: glycoside hydrolase]]
[[Category: Stick RV]]
[[Category: hydrolase]]
[[Category: Tailford LE]]
[[Category: linear free energy relationship]]
[[Category: Vasella A]]
[[Category: mannosidase]]
[[Category: transition state mimic]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr  2 11:58:39 2008''

Latest revision as of 18:25, 13 December 2023

Structural and biochemical evidence for a boat-like transition state in beta-mannosidasesStructural and biochemical evidence for a boat-like transition state in beta-mannosidases

Structural highlights

2vmf is a 2 chain structure with sequence from Bacteroides thetaiotaomicron VPI-5482. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q8AAK6_BACTN

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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[1]

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

See Also

References

  1. ↑ Tailford LE, Offen WA, Smith NL, Dumon C, Morland C, Gratien J, Heck MP, Stick RV, Bleriot Y, Vasella A, Gilbert HJ, Davies GJ. Structural and biochemical evidence for a boat-like transition state in beta-mannosidases. Nat Chem Biol. 2008 May;4(5):306-12. PMID:18408714 doi:10.1038/nchembio.81

2vmf, resolution 2.10Å

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