Phylogeny of the Vitamin K 2,3-Epoxide Reductase (VKOR) Family and Evolutionary Relationship to the Disulfide Bond Formation Protein B (DsbB) Family

Nutrients

Carville G. Bevans²  Christoph Krettler¹  Christoph Reinhart¹  Matthias Watzka³ 

[1] Department of Molecular Membrane Biology, Max Planck Institute of Biophysics, 60388 Frankfurt am Main, Germany; E-Mails:;Im Hermeshain 6, 60388 Frankfurt am Main, Germany; E-Mail:;Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, 53105 Bonn, Germany; E-Mail:

关键词: cyclic permutation;    DsbB;    homology modeling;    phylogeny;    sequence conservation;    vitamin K;    vitamin K 2;    3-epoxide;    VKOR;    VKORC1;    VKORC1L1;   

DOI  :  10.3390/nu7085281

来源: mdpi

【 摘 要 】

In humans and other vertebrate animals, vitamin K 2,3-epoxide reductase (VKOR) family enzymes are the gatekeepers between nutritionally acquired K vitamins and the vitamin K cycle responsible for posttranslational modifications that confer biological activity upon vitamin K-dependent proteins with crucial roles in hemostasis, bone development and homeostasis, hormonal carbohydrate regulation and fertility. We report a phylogenetic analysis of the VKOR family that identifies five major clades. Combined phylogenetic and site-specific conservation analyses point to clade-specific similarities and differences in structure and function. We discovered a single-site determinant uniquely identifying VKOR homologs belonging to human pathogenic, obligate intracellular prokaryotes and protists. Building on previous work by Sevier et al. (Protein Science 14:1630), we analyzed structural data from both VKOR and prokaryotic disulfide bond formation protein B (DsbB) families and hypothesize an ancient evolutionary relationship between the two families where one family arose from the other through a gene duplication/deletion event. This has resulted in circular permutation of primary sequence threading through the four-helical bundle protein folds of both families. This is the first report of circular permutation relating distant α-helical membrane protein sequences and folds. In conclusion, we suggest a chronology for the evolution of the five extant VKOR clades.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.