Histidine-tyrosine protein crosslinks

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Covalent bonds between histidine and tyrosine form in some cytochrome C oxidases[1][2][3][4][5] and catalases[6][7], making crosslinks between polypeptide chains near the catalytic sites.



  • 1gge 1999: E. coli catalase HPII.
  • 1v54 2003: Bovine heart cytochrome c oxidase.
  • 2yev 2012: Thermus thermophilus cytochrome caa3 oxidase.
  • 7coh 2021: Bovine heart cytochrome c oxidase.

Detection and Visualization

FirstGlance in Jmol automatically detects and alerts you to the presence of any of six types of covalent protein crosslinks (see list below). It provides "one click" tools to zoom in and examine any putative crosslink in detail, including display of the proximal electron density map. See the practical guide FirstGlance/Evaluating Protein Crosslinks. FirstGlance also provides a tool for clear visualization of the much more common disulfide bond crosslinks.

Other Protein Crosslinks

In addition to the bonds discussed above, other covalent cross-links between polypeptide chains include:


Thanks to Wei-Chun Kao (Univ. Freiburg, Germany) for pointing out needed corrections.

References and Notes

  1. Tsukihara T, Shimokata K, Katayama Y, Shimada H, Muramoto K, Aoyama H, Mochizuki M, Shinzawa-Itoh K, Yamashita E, Yao M, Ishimura Y, Yoshikawa S. The low-spin heme of cytochrome c oxidase as the driving element of the proton-pumping process. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15304-9. Epub 2003 Dec 12. PMID:14673090 doi:10.1073/pnas.2635097100
  2. Although His-Tyr bonds are present in 1v54 and 1v55 published by Tsukihara et al., no mention of them is made in their 2003 paper.
  3. Buse G, Soulimane T, Dewor M, Meyer HE, Bluggel M. Evidence for a copper-coordinated histidine-tyrosine cross-link in the active site of cytochrome oxidase. Protein Sci. 1999 May;8(5):985-90. PMID:10338009 doi:http://dx.doi.org/10.1110/ps.8.5.985
  4. Kaila VR, Johansson MP, Sundholm D, Laakkonen L, Wistrom M. The chemistry of the CuB site in cytochrome c oxidase and the importance of its unique His-Tyr bond. Biochim Biophys Acta. 2009 Apr;1787(4):221-33. doi: 10.1016/j.bbabio.2009.01.002. PMID:19388139 doi:http://dx.doi.org/10.1016/j.bbabio.2009.01.002
  5. Ehudin MA, Senft L, Franke A, Ivanovic-Burmazovic I, Karlin KD. Formation and Reactivity of New Isoporphyrins: Implications for Understanding the Tyr-His Cross-Link Cofactor Biogenesis in Cytochrome c Oxidase. J Am Chem Soc. 2019 Jul 10;141(27):10632-10643. doi: 10.1021/jacs.9b01791. Epub, 2019 Jun 26. PMID:31150209 doi:http://dx.doi.org/10.1021/jacs.9b01791
  6. Bravo J, Fita I, Ferrer JC, Ens W, Hillar A, Switala J, Loewen PC. Identification of a novel bond between a histidine and the essential tyrosine in catalase HPII of Escherichia coli. Protein Sci. 1997 May;6(5):1016-23. PMID:9144772 doi:http://dx.doi.org/10.1002/pro.5560060507
  7. Bravo J, Mate MJ, Schneider T, Switala J, Wilson K, Loewen PC, Fita I. Structure of catalase HPII from Escherichia coli at 1.9 A resolution. Proteins. 1999 Feb 1;34(2):155-66. doi:10.1002/(sici)1097-0134(19990201)34:2<155::aid-prot1>3.0.co;2-p. PMID:10022351

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