Identifying two ancient enzymes in archaea using predicted secondary structure alignment

ABSTRACT It is now possible to compare life forms at high levels of detail and completeness due to the increasing availability of whole genomes from all three domains. However, exploration

of interesting hypotheses requires the ability to recognize a correspondence between proteins that may since have diverged beyond the threshold of detection by sequence-based methods. Since

protein structure is far better conserved than protein sequence, structural information can enhance detection sensitivity, and this is the basis for the field of structural genomics.

Demonstrating the effectiveness of this approach, we identify two important but previously elusive Archaeal enzymes: a homolog of dihydropteroate synthase and a thymidylate synthase. The

former is especially noteworthy in that no Archaeal homolog of a bacterial folate biosynthetic enzyme has been found to date. Experimental confirmation of the deduced activity of both

enzymes is described. Identification of two different proteins was attempted deliberately to help allay concern that predictive success is merely a lucky accident. Access through your

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BEING VIEWED BY OTHERS EXPANDED DIVERSITY OF ASGARD ARCHAEA AND THEIR RELATIONSHIPS WITH EUKARYOTES Article 28 April 2021 PROTEOME-WIDE 3D STRUCTURE PREDICTION PROVIDES INSIGHTS INTO THE

ANCESTRAL METABOLISM OF ANCIENT ARCHAEA AND BACTERIA Article Open access 21 December 2022 THE ORIGIN AND RADIATION OF THE PHOSPHOPROTEIN PHOSPHATASE (PPP) ENZYMES OF EUKARYOTES Article Open

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to R.H.W. and a National Institutes of Health grant to G.D.R. We thank M.E. Rasche for running the experiments to trap the covalent complex between FdUMP and thymidylate synthase, K. Harich

for preforming the GC-MS analyses, and D. Grahame for supplying the [_methyl_-3H]-methyl-tetrahydrosarcinapterin. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Biochemistry,

Virginia Polytechnic Institute and State University, Blacksburg, 24061-0308, Virginia, USA Huimin Xu & Robert H. White * Monsanto Company, Mail Zone AA3G, 700 Chesterfield Parkway North,

St. Louis, 63198, Missouri, USA Rajeev Aurora * Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, School of Medicine, 725 N. Wolfe Street, Baltimore, 21205,

Maryland, USA George D. Rose Authors * Huimin Xu View author publications You can also search for this author inPubMed Google Scholar * Rajeev Aurora View author publications You can also

search for this author inPubMed Google Scholar * George D. Rose View author publications You can also search for this author inPubMed Google Scholar * Robert H. White View author

publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Robert H. White. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS

ARTICLE CITE THIS ARTICLE Xu, H., Aurora, R., Rose, G. _et al._ Identifying two ancient enzymes in Archaea using predicted secondary structure alignment. _Nat Struct Mol Biol_ 6, 750–754

(1999). https://doi.org/10.1038/11525 Download citation * Received: 18 November 1998 * Accepted: 13 May 1999 * Issue Date: August 1999 * DOI: https://doi.org/10.1038/11525 SHARE THIS ARTICLE

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