3lb3: Difference between revisions
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< | ==Two-site competitive inhibition in dehaloperoxidase-hemoglobin== | ||
<StructureSection load='3lb3' size='340' side='right'caption='[[3lb3]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3lb3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Amphitrite_ornata Amphitrite ornata]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LB3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4CH:4-CHLOROPHENOL'>4CH</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3lb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lb3 OCA], [https://pdbe.org/3lb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lb3 RCSB], [https://www.ebi.ac.uk/pdbsum/3lb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lb3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9NAV8_9ANNE Q9NAV8_9ANNE] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Dehaloperoxidase (DHP) from the annelid Amphitrite ornata is a catalytically active hemoglobin-peroxidase that possesses a unique internal binding cavity in the distal pocket above the heme. The previously published crystal structure of DHP shows 4-iodophenol bound internally. This led to the proposal that the internal binding site is the active site for phenol oxidation. However, the native substrate for DHP is 2,4,6-tribromophenol, and all attempts to bind 2,4,6-tribromophenol in the internal site under physiological conditions have failed. Herein, we show that the binding of 4-halophenols in the internal pocket inhibits enzymatic function. Furthermore, we demonstrate that DHP has a unique two-site competitive binding mechanism in which the internal and external binding sites communicate through two conformations of the distal histidine of the enzyme, resulting in nonclassical competitive inhibition. The same distal histidine conformations involved in DHP function regulate oxygen binding and release during transport and storage by hemoglobins and myoglobins. This work provides further support for the hypothesis that DHP possesses an external binding site for substrate oxidation, as is typical for the peroxidase family of enzymes. | |||
Internal binding of halogenated phenols in dehaloperoxidase-hemoglobin inhibits peroxidase function.,Thompson MK, Davis MF, de Serrano V, Nicoletti FP, Howes BD, Smulevich G, Franzen S Biophys J. 2010 Sep 8;99(5):1586-95. PMID:20816071<ref>PMID:20816071</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3lb3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Dehaloperoxidase 3D structures|Dehaloperoxidase 3D structures]] | |||
*[[Hemoglobin 3D structures|Hemoglobin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
== | </StructureSection> | ||
== | |||
< | |||
[[Category: Amphitrite ornata]] | [[Category: Amphitrite ornata]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Davis MF]] | ||
[[Category: | [[Category: Franzen S]] | ||
[[Category: | [[Category: Howes BD]] | ||
[[Category: | [[Category: Nicoletti FP]] | ||
[[Category: Smulevich | [[Category: Smulevich G]] | ||
[[Category: Thompson | [[Category: Thompson MK]] | ||
[[Category: | [[Category: De Serrano VS]] | ||
Latest revision as of 11:33, 6 September 2023
Two-site competitive inhibition in dehaloperoxidase-hemoglobinTwo-site competitive inhibition in dehaloperoxidase-hemoglobin
Structural highlights
FunctionPublication Abstract from PubMedDehaloperoxidase (DHP) from the annelid Amphitrite ornata is a catalytically active hemoglobin-peroxidase that possesses a unique internal binding cavity in the distal pocket above the heme. The previously published crystal structure of DHP shows 4-iodophenol bound internally. This led to the proposal that the internal binding site is the active site for phenol oxidation. However, the native substrate for DHP is 2,4,6-tribromophenol, and all attempts to bind 2,4,6-tribromophenol in the internal site under physiological conditions have failed. Herein, we show that the binding of 4-halophenols in the internal pocket inhibits enzymatic function. Furthermore, we demonstrate that DHP has a unique two-site competitive binding mechanism in which the internal and external binding sites communicate through two conformations of the distal histidine of the enzyme, resulting in nonclassical competitive inhibition. The same distal histidine conformations involved in DHP function regulate oxygen binding and release during transport and storage by hemoglobins and myoglobins. This work provides further support for the hypothesis that DHP possesses an external binding site for substrate oxidation, as is typical for the peroxidase family of enzymes. Internal binding of halogenated phenols in dehaloperoxidase-hemoglobin inhibits peroxidase function.,Thompson MK, Davis MF, de Serrano V, Nicoletti FP, Howes BD, Smulevich G, Franzen S Biophys J. 2010 Sep 8;99(5):1586-95. PMID:20816071[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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