View source for 7xma


==Crystal structure of Bovine heart cytochrome c oxidase, apo structure with DMSO==
<StructureSection load='7xma' size='340' side='right'caption='[[7xma]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7xma]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XMA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XMA 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene>, <scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=CU:COPPER+(II)+ION'>CU</scene>, <scene name='pdbligand=CUA:DINUCLEAR+COPPER+ION'>CUA</scene>, <scene name='pdbligand=DMU:DECYL-BETA-D-MALTOPYRANOSIDE'>DMU</scene>, <scene name='pdbligand=FME:N-FORMYLMETHIONINE'>FME</scene>, <scene name='pdbligand=HEA:HEME-A'>HEA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEK:(1S)-2-{[(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(STEAROYLOXY)METHYL]ETHYL+(5E,8E,11E,14E)-ICOSA-5,8,11,14-TETRAENOATE'>PEK</scene>, <scene name='pdbligand=PER:PEROXIDE+ION'>PER</scene>, <scene name='pdbligand=PGV:(1R)-2-{[{[(2S)-2,3-DIHYDROXYPROPYL]OXY}(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL+(11E)-OCTADEC-11-ENOATE'>PGV</scene>, <scene name='pdbligand=PSC:(7R,17E,20E)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSA-17,20-DIEN-1-AMINIUM+4-OXIDE'>PSC</scene>, <scene name='pdbligand=TGL:TRISTEAROYLGLYCEROL'>TGL</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7xma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xma OCA], [https://pdbe.org/7xma PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xma RCSB], [https://www.ebi.ac.uk/pdbsum/7xma PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xma ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/COX1_BOVIN COX1_BOVIN] Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Subunits 1-3 form the functional core of the enzyme complex. CO I is the catalytic subunit of the enzyme. Electrons originating in cytochrome c are transferred via the copper A center of subunit 2 and heme A of subunit 1 to the bimetallic center formed by heme A3 and copper B.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Antimicrobial resistance (AMR) is a global health problem. Despite the enormous efforts made in the last decade, threats from some species, including drug-resistant Neisseria gonorrhoeae, continue to rise and would become untreatable. The development of antibiotics with a different mechanism of action is seriously required. Here, we identified an allosteric inhibitory site buried inside eukaryotic mitochondrial heme-copper oxidases (HCOs), the essential respiratory enzymes for life. The steric conformation around the binding pocket of HCOs is highly conserved among bacteria and eukaryotes, yet the latter has an extra helix. This structural difference in the conserved allostery enabled us to rationally identify bacterial HCO-specific inhibitors: an antibiotic compound against ceftriaxone-resistant Neisseria gonorrhoeae. Molecular dynamics combined with resonance Raman spectroscopy and stopped-flow spectroscopy revealed an allosteric obstruction in the substrate accessing channel as a mechanism of inhibition. Our approach opens fresh avenues in modulating protein functions and broadens our options to overcome AMR.

Identifying antibiotics based on structural differences in the conserved allostery from mitochondrial heme-copper oxidases.,Nishida Y, Yanagisawa S, Morita R, Shigematsu H, Shinzawa-Itoh K, Yuki H, Ogasawara S, Shimuta K, Iwamoto T, Nakabayashi C, Matsumura W, Kato H, Gopalasingam C, Nagao T, Qaqorh T, Takahashi Y, Yamazaki S, Kamiya K, Harada R, Mizuno N, Takahashi H, Akeda Y, Ohnishi M, Ishii Y, Kumasaka T, Murata T, Muramoto K, Tosha T, Shiro Y, Honma T, Shigeta Y, Kubo M, Takashima S, Shintani Y Nat Commun. 2022 Dec 8;13(1):7591. doi: 10.1038/s41467-022-34771-y. PMID:36481732<ref>PMID:36481732</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xma" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Large Structures]]
[[Category: Kumasaka T]]
[[Category: Mizuno N]]
[[Category: Nishida Y]]
[[Category: Shintani Y]]
[[Category: Shinzawa-Itoh K]]
[[Category: Takashima S]]
[[Category: Tsukihara T]]
[[Category: Yoshikawa S]]