Catalytic center of cytochrome c oxidase: Effects of protein environment on pKa values of cub histidine ligands
The molecular mechanism by which electron transfer (ET) is coupled to proton pumping in cytochrome oxidase is one of the main unsolved problems in biochemistry. Particularly, the nature and position of the proton-loading site is under dispute. The CuB complex has three ligated histidines, whereas on...
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| Format: | Article |
| Language: | English |
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Serbian Chemical Society
2020-01-01
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| Series: | Journal of the Serbian Chemical Society |
| Subjects: | |
| Online Access: | http://www.doiserbia.nb.rs/img/doi/0352-5139/2020/0352-51392000047P.pdf |
| _version_ | 1831650464829014016 |
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| author | Popović Dragan M. Đorđević Ivana S. |
| author_facet | Popović Dragan M. Đorđević Ivana S. |
| author_sort | Popović Dragan M. |
| collection | DOAJ |
| description | The molecular mechanism by which electron transfer (ET) is coupled to proton pumping in cytochrome oxidase is one of the main unsolved problems in biochemistry. Particularly, the nature and position of the proton-loading site is under dispute. The CuB complex has three ligated histidines, whereas only His290 and His291 are ionizable sites with the same pKa values in aqueous solution, but apparently quite different ones within the enzyme. Earlier, a model of proton pumping with the central role of His290 was proposed. Recent calculations indicate that the His291 ligand of the CuB center might play the role of the pumping element, since its protonation state depends on the oxidation state of the binuclear complex (BNC). The present electrostatic study was applied to assess the role of the protein environment on the acidity of the two histidines. Their pKa values and effects of different energy terms were evaluated to discover the nature of their diverse behavior in the enzyme. Here, a new set of pKa values for the non-standard model compounds within the BNC was applied. The enhanced results are compared with results of previous studies in the light of the plausible proton pumping mechanism. The obtained microscopic and apparent pKa values in the oxidized state of BNC are virtually the same, indicating that deprotonated form of His291 accounts for the large pKa increase of His290, since then both titratable sites on then CuB center cannot simultaneously be in the charged state. The present results support the underlined His291 pumping model. |
| first_indexed | 2024-12-19T15:11:13Z |
| format | Article |
| id | doaj.art-441e13b8c59748029c29c9abd395544c |
| institution | Directory Open Access Journal |
| issn | 0352-5139 1820-7421 |
| language | English |
| last_indexed | 2024-12-19T15:11:13Z |
| publishDate | 2020-01-01 |
| publisher | Serbian Chemical Society |
| record_format | Article |
| series | Journal of the Serbian Chemical Society |
| spelling | doaj.art-441e13b8c59748029c29c9abd395544c2022-12-21T20:16:18ZengSerbian Chemical SocietyJournal of the Serbian Chemical Society0352-51391820-74212020-01-0185111429144410.2298/JSC200720047P0352-51392000047PCatalytic center of cytochrome c oxidase: Effects of protein environment on pKa values of cub histidine ligandsPopović Dragan M.0Đorđević Ivana S.1Institute of Chemistry, Technology and Metallurgy, Department of Chemistry, University of Belgrade, Belgrade, SerbiaInstitute of Chemistry, Technology and Metallurgy, Department of Chemistry, University of Belgrade, Belgrade, SerbiaThe molecular mechanism by which electron transfer (ET) is coupled to proton pumping in cytochrome oxidase is one of the main unsolved problems in biochemistry. Particularly, the nature and position of the proton-loading site is under dispute. The CuB complex has three ligated histidines, whereas only His290 and His291 are ionizable sites with the same pKa values in aqueous solution, but apparently quite different ones within the enzyme. Earlier, a model of proton pumping with the central role of His290 was proposed. Recent calculations indicate that the His291 ligand of the CuB center might play the role of the pumping element, since its protonation state depends on the oxidation state of the binuclear complex (BNC). The present electrostatic study was applied to assess the role of the protein environment on the acidity of the two histidines. Their pKa values and effects of different energy terms were evaluated to discover the nature of their diverse behavior in the enzyme. Here, a new set of pKa values for the non-standard model compounds within the BNC was applied. The enhanced results are compared with results of previous studies in the light of the plausible proton pumping mechanism. The obtained microscopic and apparent pKa values in the oxidized state of BNC are virtually the same, indicating that deprotonated form of His291 accounts for the large pKa increase of His290, since then both titratable sites on then CuB center cannot simultaneously be in the charged state. The present results support the underlined His291 pumping model.http://www.doiserbia.nb.rs/img/doi/0352-5139/2020/0352-51392000047P.pdfbioenergeticsbinuclear complexbovinehistidine ligandslinear poisson-boltzmann equationpka calculationsreaction and protein field |
| spellingShingle | Popović Dragan M. Đorđević Ivana S. Catalytic center of cytochrome c oxidase: Effects of protein environment on pKa values of cub histidine ligands Journal of the Serbian Chemical Society bioenergetics binuclear complex bovine histidine ligands linear poisson-boltzmann equation pka calculations reaction and protein field |
| title | Catalytic center of cytochrome c oxidase: Effects of protein environment on pKa values of cub histidine ligands |
| title_full | Catalytic center of cytochrome c oxidase: Effects of protein environment on pKa values of cub histidine ligands |
| title_fullStr | Catalytic center of cytochrome c oxidase: Effects of protein environment on pKa values of cub histidine ligands |
| title_full_unstemmed | Catalytic center of cytochrome c oxidase: Effects of protein environment on pKa values of cub histidine ligands |
| title_short | Catalytic center of cytochrome c oxidase: Effects of protein environment on pKa values of cub histidine ligands |
| title_sort | catalytic center of cytochrome c oxidase effects of protein environment on pka values of cub histidine ligands |
| topic | bioenergetics binuclear complex bovine histidine ligands linear poisson-boltzmann equation pka calculations reaction and protein field |
| url | http://www.doiserbia.nb.rs/img/doi/0352-5139/2020/0352-51392000047P.pdf |
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