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2rht

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Revision as of 04:36, 10 February 2016

Crystal Structure of the S112A mutant of a C-C hydrolase, BphD from Burkholderia xenovorans LB400, in complex with 3-Cl HOPDA

Structural highlights

2rht is a 1 chain structure with sequence from Burkholderia xenovorans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	2puh, 2puj, 2rhw
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[BPHD_BURXL] Catalyzes an unusual C-C bond hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) to produce benzoic acid and 2-hydroxy-2,4-pentadienoic acid (HPD).^[1]

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

The microbial degradation of polychlorinated biphenyls (PCBs) by the biphenyl catabolic (Bph) pathway is limited in part by the pathway's fourth enzyme, BphD. BphD catalyzes an unusual carbon-carbon bond hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA), in which the substrate is subject to histidine-mediated enol-keto tautomerization prior to hydrolysis. Chlorinated HOPDAs such as 3-Cl HOPDA inhibit BphD. Here we report that BphD preferentially hydrolyzed a series of 3-substituted HOPDAs in the order H>F>Cl>Me, suggesting that catalysis is affected by steric, not electronic, determinants. Transient state kinetic studies performed using wild-type BphD and the hydrolysis-defective S112A variant indicated that large 3-substituents inhibited His-265-catalyzed tautomerization by 5 orders of magnitude. Structural analyses of S112A.3-Cl HOPDA and S112A.3,10-diF HOPDA complexes revealed a non-productive binding mode in which the plane defined by the carbon atoms of the dienoate moiety of HOPDA is nearly orthogonal to that of the proposed keto tautomer observed in the S112A.HOPDA complex. Moreover, in the 3-Cl HOPDA complex, the 2-hydroxo group is moved by 3.6 A from its position near the catalytic His-265 to hydrogen bond with Arg-190 and access of His-265 is blocked by the 3-Cl substituent. Nonproductive binding may be stabilized by interactions involving the 3-substituent with non-polar side chains. Solvent molecules have poor access to C6 in the S112A.3-Cl HOPDA structure, more consistent with hydrolysis occurring via an acyl-enzyme than a gem-diol intermediate. These results provide insight into engineering BphD for PCB degradation.

The molecular basis for inhibition of BphD, a C-C bond hydrolase involved in polychlorinated biphenyls degradation: large 3-substituents prevent tautomerization.,Bhowmik S, Horsman GP, Bolin JT, Eltis LD J Biol Chem. 2007 Dec 14;282(50):36377-85. Epub 2007 Oct 11. PMID:17932031^[2]

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

References

↑ Horsman GP, Ke J, Dai S, Seah SY, Bolin JT, Eltis LD. Kinetic and structural insight into the mechanism of BphD, a C-C bond hydrolase from the biphenyl degradation pathway. Biochemistry. 2006 Sep 19;45(37):11071-86. PMID:16964968 doi:10.1021/bi0611098
↑ Bhowmik S, Horsman GP, Bolin JT, Eltis LD. The molecular basis for inhibition of BphD, a C-C bond hydrolase involved in polychlorinated biphenyls degradation: large 3-substituents prevent tautomerization. J Biol Chem. 2007 Dec 14;282(50):36377-85. Epub 2007 Oct 11. PMID:17932031 doi:10.1074/jbc.M707035200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2rht"

@@ Line 5: / Line 5: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C1E:(2Z,4E)-3-CHLORO-2-HYDROXY-6-OXO-6-PHENYLHEXA-2,4-DIENOIC+ACID'>C1E</scene>, <scene name='pdbligand=MLI:MALONATE+ION'>MLI</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2puh|2puh]], [[2puj|2puj]], [[2rhw|2rhw]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rht OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2rht RCSB], [http://www.ebi.ac.uk/pdbsum/2rht PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2rht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rht OCA], [http://pdbe.org/2rht PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rht RCSB], [http://www.ebi.ac.uk/pdbsum/2rht PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 17: @@
     <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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2rht ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 27: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2rht" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2rht

From Proteopedia

Revision as of 04:36, 10 February 2016

Crystal Structure of the S112A mutant of a C-C hydrolase, BphD from Burkholderia xenovorans LB400, in complex with 3-Cl HOPDA

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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