View source for 3ozw


==The Crystal Structure of flavohemoglobin from R. eutrophus in complex with ketoconazole==
<StructureSection load='3ozw' size='340' side='right'caption='[[3ozw]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3ozw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cupriavidus_necator_H16 Cupriavidus necator H16]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OZW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OZW 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]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DGG:1-[GLYCEROLYLPHOSPHONYL]-2-[8-(2-HEXYL-CYCLOPROPYL)-OCTANAL-1-YL]-3-[HEXADECANAL-1-YL]-GLYCEROL'>DGG</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=KKK:1-ACETYL-4-(4-{[(2R,4S)-2-(2,4-DICHLOROPHENYL)-2-(1H-IMIDAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL]METHOXY}PHENYL)PIPERAZINE'>KKK</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=3ozw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ozw OCA], [https://pdbe.org/3ozw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ozw RCSB], [https://www.ebi.ac.uk/pdbsum/3ozw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ozw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HMP_CUPNH HMP_CUPNH] Is involved in NO detoxification in an aerobic process, termed nitric oxide dioxygenase (NOD) reaction that utilizes O(2) and NAD(P)H to convert NO to nitrate, which protects the bacterium from various noxious nitrogen compounds. Therefore, plays a central role in the inducible response to nitrosative stress.  In the presence of oxygen and NADH, FHP has NADH oxidase activity, which leads to the generation of superoxide and H(2)O(2), both in vitro and in vivo, and it has been suggested that FHP might act as an amplifier of superoxide stress. Under anaerobic conditions, FHP also exhibits nitric oxide reductase and FAD reductase activities. However, all these reactions are much lower than NOD activity.
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== Publication Abstract from PubMed ==
Flavohemoglobins (flavoHbs) are enzymes that operate primarily as nitric oxide dioxygenases and shuttle thereby electrons among NAD(P)H, FAD, heme, and a ligated redox-active substrate such as O(2). They function in the bacterial defense against nitrosative stress and are therefore considered as targets for new antibiotic drugs. Recently, azole derivatives were proven to be attractive nitric oxide dioxygenase inhibitors, and to explore their binding characteristics, we determined the X-ray structure of the flavoHb from Ralstonia eutropha in a complex with miconazole (FHP(M)), econazole (FHP(E)), and ketoconazole (FHP(K)). In agreement with UV-vis spectroscopic data, one azole compound binds inside the distal heme pocket and ligates to the heme iron by its imidazole substituent. The two additional substituents, mostly chlorinated phenyl groups, form a series of van der Waals contacts with the protein matrix. Both interactions explain their high affinity for flavoHbs, the binding constants being 2.6, 1.2, and 11.6 muM for miconazole, econazole, and ketoconazole, respectively. The FHP(M) and FHP(Lip) (flavoHbs originally loaded with a phospholipid) structures share an "open" state and the FHP(E) and FHP(K) structures a "closed" state. Although the azole compounds were able to push the lipid out of its binding site, a fatty acid fragment is still bound inside the heme pocket of FHP(E) and FHP(K) and dictates the state of the protein. The ligand-induced open-to-closed transition involves a reorientation of the NADH domain accompanied by conformational changes in the C-terminal arm, helix E, and the CE loop resulting in an encapsulation of the heme-binding pocket. Implications of the observed open-to-closed process on the catalytic cycle are discussed.

Structure of Ralstonia eutropha Flavohemoglobin in Complex with Three Antibiotic Azole Compounds.,El Hammi E, Warkentin E, Demmer U, Limam F, Marzouki NM, Ermler U, Baciou L Biochemistry. 2011 Feb 22;50(7):1255-1264. Epub 2011 Jan 20. PMID:21210640<ref>PMID:21210640</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3ozw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hemoglobin 3D structures|Hemoglobin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Cupriavidus necator H16]]
[[Category: Large Structures]]
[[Category: Baciou L]]
[[Category: Demmer U]]
[[Category: El Hammi E]]
[[Category: Ermler U]]
[[Category: Warkentin E]]