Evolutionary migration of a post-translationally modified active-site residue in the proton-pumping heme-copper oxygen reductases

James Hemp, Dana E. Robinson, Krithika B. Ganesan, Todd J. Martinez, Neil L. Kelleher, Robert B. Gennis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

In the respiratory chains of aerobic organisms, oxygen reductase members of the heme-copper superfamily couple the reduction of O2 to proton pumping, generating an electrochemical gradient. There are three distinct families of heme-copper oxygen reductases: A, B, and C types. The A- and B-type oxygen reductases have an active-site tyrosine that forms a unique cross-linked histidine-tyrosine cofactor. In the C-type oxygen reductases (also called cbb3 oxidases), an analogous active-site tyrosine has recently been predicted by molecular modeling to be located within a different transmembrane helix in comparison to the A- and B-type oxygen reductases. In this work, Fourier-transform mass spectrometry is used to show that the predicted tyrosine forms a histidine-tyrosine cross-linked cofactor in the active site of the C-type oxygen reductases. This is the first known example of the evolutionary migration of a post-translationally modified active-site residue. It also verifies the presence of a unique cofactor in all three families of proton-pumping respiratory oxidases, demonstrating that these enzymes likely share a common reaction mechanism and that the histidine-tyrosine cofactor may be a required component for proton pumping.

Original languageEnglish (US)
Pages (from-to)15405-15410
Number of pages6
JournalBiochemistry
Volume45
Issue number51
DOIs
StatePublished - Dec 26 2006

ASJC Scopus subject areas

  • Biochemistry

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