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| | {{STRUCTURE_2rht| PDB=2rht | SCENE= }} | | {{STRUCTURE_2rht| PDB=2rht | SCENE= }} |
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| - | '''Crystal Structure of the S112A mutant of a C-C hydrolase, BphD from Burkholderia xenovorans LB400, in complex with 3-Cl HOPDA'''
| + | ===Crystal Structure of the S112A mutant of a C-C hydrolase, BphD from Burkholderia xenovorans LB400, in complex with 3-Cl HOPDA=== |
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| - | ==Overview==
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| - | 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 line below this paragraph, {{ABSTRACT_PUBMED_17932031}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17932031 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17932031}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: C-c bond hydrolase]] | | [[Category: C-c bond hydrolase]] |
| | [[Category: Hydrolase]] | | [[Category: Hydrolase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 16:55:57 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 21:09:02 2008'' |
Revision as of 18:09, 28 July 2008
Template:STRUCTURE 2rht
Crystal Structure of the S112A mutant of a C-C hydrolase, BphD from Burkholderia xenovorans LB400, in complex with 3-Cl HOPDA
Template:ABSTRACT PUBMED 17932031
About this Structure
2RHT is a Single protein structure of sequence from Burkholderia xenovorans. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Jul 28 21:09:02 2008
