Matthew Hj Cordes

Matthew Hj Cordes

Associate Professor, Chemistry and Biochemistry-Sci
Associate Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(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.

Publications

Bull, H. G., Thornberry, N. A., Cordes, M. H., & Patchett, A. A. (1985). Inhibition of rabbit lung angiotensin-converting enzyme by N(α)-[(S)-1-carboxy-3-phenylpropyl]L-alanyl-L-proline and N(α)-[(S)-1-carboxy-3-phenylpropyl]L-lysyl-L-proline. Journal of Biological Chemistry, 260(5), 2952-2962.

PMID: 2982845;Abstract:

Two novel peptide analogs, N(α)-[(S)-1-carboxy-3-phenylpropyl]L-alanyl-L-proline and the corresponding L-lysyl-L-proline derivative, have been demonstrated to be potent competitive inhibitors of purified rabbit lung angiotensin-converting enzyme: K(i) = 2 and 1 x 10-10 M, respectively, at pH 7.5, 25°C, and 0.3 M chloride ion. Second-order rate constants for addition of these inhibitors to enzyme under the same conditions are in the range 1-2 x 106 M-1 s-1; first-order rate constants for dissociation of the EI complexes are in the range 1-4 x 10-4 s-1. The association rate constants are similar to those measured for D-3-mercapto-2-methylpropanoyl-L-proline, captopril, but the dissociation rate constants are severalfold slower and account for the higher affinity of these inhibitors for the enzyme. The dissociation constant for the EI complex containing N(α)-[(S)-1-carboxy-3-phenylpropyl]L-alanyl-L-proline is pH-dependent, and reaches a minimum at approximately pH 6: K(i) = 4 ± 1 x 10-11 M. The pH dependence is consistent either with a model for which the protonation state of the secondary nitrogen atom in the inhibitor determines binding affinity, or one for which ionizations on the enzyme alone influence affinity for these inhibitors. The affinity of this inhibitor for the zinc-free apoenzyme is 2 x 104 times less than that for the holoenzyme. If considered as a 'collected product' inhibitor, N(α)-[(S)-1-carboxy-3-phenylprolyl]L-alanyl-L-proline appears to derive an additional factor of 375 M in its affinity for the enzyme compared to that of the two products of its hypothetical hydrolysis, a consequence of favorably entropy effects.

Bouvignies, G., Korzhnev, D. M., Neudecker, P., Hansen, D. F., H., M., & Kay, L. E. (2010). A simple method for measuring signs of 1HN chemical shift differences between ground and excited protein states. Journal of Biomolecular NMR, 47(2), 135-141.

PMID: 20428928;PMCID: PMC3034452;Abstract:

NMR relaxation dispersion spectroscopy is a powerful method for studying protein conformational dynamics whereby visible, ground and invisible, excited conformers interconvert on the millisecond time-scale. In addition to providing kinetics and thermodynamics parameters of the exchange process, the CPMG dispersion experiment also allows extraction of the absolute values of the chemical shift differences between interconverting states, |δω̄|, opening the way for structure determination of excited state conformers. Central to the goal of structural analysis is the availability of the chemical shifts of the excited state that can only be obtained once the signs of δω̄ are known. Herein we describe a very simple method for determining the signs of 1HN δω̄ values based on a comparison of peak positions in the directly detected dimensions of a pair of 1HN-15N correlation maps recorded at different static magnetic fields. The utility of the approach is demonstrated for three proteins that undergo millisecond time-scale conformational rearrangements. Although the method provides fewer signs than previously published techniques it does have a number of strengths: (1) Data sets needed for analysis are typically available from other experiments, such as those required for measuring signs of 15N δω̄ values, thus requiring no additional experimental time, (2) acquisition times in the critical detection dimension can be as long as necessary and (3) the signs obtained can be used to cross-validate those from other approaches. © Springer Science+Business Media B.V. 2010.

LeFevre, K. R., & Cordes, M. H. (2003). Retroevolution of lambda Cro toward a stable monomer. Proceedings of the National Academy of Sciences of the United States of America, 100(5).

The Cro protein from bacteriophage lambda has a dimeric alpha+beta fold that evolved from an ancestral all-alpha monomer. The sequence mutations responsible for this dramatic structural evolution are unknown. Here we use analysis of sequence alignments to show that Ala-33, a small side chain in the hydrophobic "ball-and-socket" dimer interface of lambda Cro, was a much larger tryptophan side chain at a previous point in evolution. The retroevolutionary lambda Cro-A33W mutant shows a 10-fold reduction in dimerization affinity relative to the wild type as well as a large increase in monomer thermal stability (Delta T(m) > 10 degrees C), apparently due to partial filling of the hydrophobic socket from within the same monomer. An additional mutation in the dimer interface, F58D, almost completely abolishes detectable dimerization while maintaining the high monomer stability. The secondary structure content of the monomerized versions of lambda Cro is similar to that of the wild-type protein, and the tertiary structure of the monomer appears relatively well defined. These results (i) support a model in which the ball-and-socket dimer interface of lambda Cro was created by altered volume mutations within a limited branch of the Cro lineage and (ii) suggest the possibility that the evolution of the alpha+beta dimer from an all-alpha monomer proceeded through an alpha+beta monomer intermediate.

Cordes, M. H., & Binford, G. J. (2006). Lateral gene transfer of a dermonecrotic toxin between spiders and bacteria. Bioinformatics, 22(3), 264-268.

PMID: 16332712;Abstract:

Motivation: Spiders in the genus Loxosceles, including the notoriously toxic brown recluse, cause severe necrotic skin lesions owing to the presence of a venom enzyme called sphingomyelinase D (SMaseD). This enzyme activity is unknown elsewhere in the animal kingdom but is shared with strains of pathogenic Corynebacteria that cause various illnesses in farm animals. The presence of the same toxic activity only in distantly related organisms poses an interesting and medically important question in molecular evolution. Results: We use superpositions of rece ntly determined structures and sequence comparisons to infer that both bacterial and spider SMaseDs originated from a common, broadly conserved domain family, the glycerophosphoryl diester phosphodiesterases. We also identify a unique sequence/structure motif present in both SMaseDs but not in the ancestral family, supporting SMaseD origin through a single divergence event in either bacteria or spiders, followed by lateral gene transfer from one lineage to the other. © The Author 2005. Published by Oxford University Press. All rights reserved.

Dubrava, M. S., Ingram, W. M., Roberts, S. A., Weichsel, A., Montfort, W. R., & Cordes, M. H. (2008). N15 Cro and lambda Cro: orthologous DNA-binding domains with completely different but equally effective homodimer interfaces. Protein Science, 17(5).

Bacteriophage Cro proteins bind to target DNA as dimers but do not all dimerize with equal strength, and differ in fold in the region of the dimer interface. We report the structure of the Cro protein from Enterobacteria phage N15 at 1.05 A resolution. The subunit fold contains five alpha-helices and is closely similar to the structure of P22 Cro (1.3 A backbone room mean square difference over 52 residues), but quite different from that of lambda Cro, a structurally diverged member of this family with a mixed alpha-helix/beta-sheet fold. N15 Cro crystallizes as a biological dimer with an extensive interface (1303 A(2) change in accessible surface area per dimer) and also dimerizes in solution with a K(d) of 5.1 +/- 1.5 microM. Its dimerization is much stronger than that of its structural homolog P22 Cro, which does not self-associate detectably in solution. Instead, the level of self-association and interfacial area for N15 Cro is similar to that of lambda Cro, even though these two orthologs do not share the same fold and have dimer interfaces that are qualitatively different in structure. The common Cro ancestor is thought to be an all-helical monomer similar to P22 Cro. We propose that two Cro descendants independently developed stronger dimerization by entirely different mechanisms.