Matthew Hj Cordes

Matthew Hj Cordes

Associate Professor, Chemistry and Biochemistry-Sci
Associate Professor, BIO5 Institute
Primary Department
Department Affiliations
(520) 626-1175

Research Interest

Matthew Cordes, Ph.D. is an Associate Professor of Chemistry and Biochemistry at the University of Arizona College of Science. Dr. Cordes’ research focuses on the origin and evolution of new protein structures and functions. He has published approximately 30 original research papers and presents his work frequently at national meetings such as the Protein Society and Gordon Research Conferences on Proteins and Biopolymers. Dr. Cordes’ primary research contributions are in four fields of protein evolution. First, his laboratory has identified cases in which a new type of protein structure has evolved from a preexisting structure. Second, he has identified evolutionary codes by which proteins that bind specific sites on double-stranded DNA evolve to recognize new target sites. Third, he studies the evolution of proteins in bloodsucking insects and spiders that affect blood homeostasis or cause dermonecrotic effects in mammalian tissue. Finally, he uses bioinformatics to identify hidden patterns in protein sequences that allow them to fold correctly and avoid aggregation such as that which occurs in Alzheimer’s disease. Dr. Cordes presently holds a BIO5 pilot project seed grant to study the evolution of enzyme toxins in brown spider venom.


Lajoie, D. M., Zobel-Thropp, P. A., Kumirov, V. K., Bandarian, V., Binford, G. J., & Cordes, M. H. (2013). Phospholipase D toxins of brown spider venom convert lysophosphatidylcholine and sphingomyelin to cyclic phosphates. PLoS ONE, 8(8).

Venoms of brown spiders in the genus Loxosceles contain phospholipase D enzyme toxins that can cause severe dermonecrosis and even death in humans. These toxins cleave the substrates sphingomyelin and lysophosphatidylcholine in mammalian tissues, releasing the choline head group. The other products of substrate cleavage have previously been reported to be monoester phospholipids, which would result from substrate hydrolysis. Using (31)P NMR and mass spectrometry we demonstrate that recombinant toxins, as well as whole venoms from diverse Loxosceles species, exclusively catalyze transphosphatidylation rather than hydrolysis, forming cyclic phosphate products from both major substrates. Cyclic phosphates have vastly different biological properties from their monoester counterparts, and they may be relevant to the pathology of brown spider envenomation.

McKnight, C. J., & Cordes, M. H. (2005). Networking at the Protein Society symposium.. Nature Chemical Biology, 1(5), 239-242.

PMID: 16408046;Abstract:

From the complex behavior of multicomponent signaling networks to the structures of large protein complexes and aggregates, questions once viewed as daunting are now being tackled fearlessly by protein scientists. The 19th Annual Symposium of the Protein Society in Boston highlighted the maturation of systems biology as applied to proteins.

Andreatta, M. E., Levine, J. A., Foy, S. G., Guzman, L. D., Kosinski, L. J., Cordes, M. H., & Masel, J. (2015). The Recent De Novo Origin of Protein C-Termini. Genome biology and evolution, 7(6), 1686-701.
BIO5 Collaborators
Matthew Hj Cordes, Joanna Masel

Protein-coding sequences can arise either from duplication and divergence of existing sequences, or de novo from noncoding DNA. Unfortunately, recently evolved de novo genes can be hard to distinguish from false positives, making their study difficult. Here, we study a more tractable version of the process of conversion of noncoding sequence into coding: the co-option of short segments of noncoding sequence into the C-termini of existing proteins via the loss of a stop codon. Because we study recent additions to potentially old genes, we are able to apply a variety of stringent quality filters to our annotations of what is a true protein-coding gene, discarding the putative proteins of unknown function that are typical of recent fully de novo genes. We identify 54 examples of C-terminal extensions in Saccharomyces and 28 in Drosophila, all of them recent enough to still be polymorphic. We find one putative gene fusion that turns out, on close inspection, to be the product of replicated assembly errors, further highlighting the issue of false positives in the study of rare events. Four of the Saccharomyces C-terminal extensions (to ADH1, ARP8, TPM2, and PIS1) that survived our quality filters are predicted to lead to significant modification of a protein domain structure.

Stewart, K. L., Nelson, M. R., Eaton, K. V., Anderson, W. J., & Cordes, M. H. (2013). A role for indels in the evolution of Cro protein folds. Proteins, 81(11).

Insertions and deletions in protein sequences, or indels, can disrupt structure and may result in changes in protein folds during evolution or in association with alternative splicing. Pfl 6 and Xfaso 1 are two proteins in the Cro family that share a common ancestor but have different folds. Sequence alignments of the two proteins show two gaps, one at the N terminus, where the sequence of Xfaso 1 is two residues shorter, and one near the center of the sequence, where the sequence of Pfl 6 is five residues shorter. To test the potential importance of indels in Cro protein evolution, we generated hybrid variants of Pfl 6 and Xfaso 1 with indels in one or both regions, chosen according to several plausible sequence alignments. All but one deletion variant completely unfolded both proteins, showing that a longer N-terminal sequence was critical for Pfl 6 folding and a longer central region sequence was critical for Xfaso 1 folding. By contrast, Xfaso 1 tolerated a longer N-terminal sequence with little destabilization, and Pfl 6 tolerated central region insertions, albeit with substantial effects on thermal stability and some perturbation of the surrounding structure. None of the mutations appeared to convert one stable fold into the other. On the basis of this two-protein comparison, short insertion and deletion mutations probably played a role in evolutionary fold change in the Cro family, but were also not the only factors. Proteins 2013; 81:1988-1996. © 2013 Wiley Periodicals, Inc.

H., M., Gala, S. D., & Berson, J. A. (1994). Stereochemistry of a cyclopropanone by crystal structure analysis. The exo configuration of the diels-alder adduct of cyclopropenone and 1,3-diphenylisobenzofuran appears to be stabilized relative to the endo by an attractive ether-carbonyl interaction. Journal of the American Chemical Society, 116(24), 11161-11162.