About

Matthew Cordes is an Associate Professor at the University of Arizona, within the Department of Chemistry and Biochemistry. He holds a B.S. degree from Bowdoin College, obtained between 1983 and 1987, and a Ph.D. from Yale University, completed between 1987 and 1997. He also completed a postdoctoral fellowship at MIT from 1994 to 2000. His research specialties include biophysics, protein and membrane biochemistry, spectroscopy/molecular structure, and structural biology. His research focuses on molecular evolution in the post-genome age of biology. With the advent of extensive genome sequencing projects and the growth of biomolecular structure databases, his work aims to comprehensively understand and study the diversity and diversification of biological molecules.

Research topics

• Computer Science
• Ecology
• Biology
• Biochemistry
• Chemistry
• Political Science
• Philosophy
• Cell biology
• Law
• Stereochemistry
• Computational biology

Selected publications

• How does spider venom damage human cells? Researchers uncover the killer mechanism of recluse spider toxin

  2026-04-06

  article1st authorCorresponding
  PublisherDOI

• Spider venom phospholipase D toxin structure: Interfacial binding site, mechanism, activation, and head group preference

  Proceedings of the National Academy of Sciences · 2026-04-06

  articleOpen accessSenior authorCorresponding

  Envenomation by sicariid spiders such as the brown recluse can cause loxoscelism, a syndrome involving localized dermonecrosis and/or systemic effects like hemolysis. The causative venom toxins are unusual interfacial phospholipase D enzymes that cyclize sphingolipid and lysophospholipid substrates when bound to membrane surfaces. Crystal structures of several of these toxins have been reported, but none of them directly illuminates how lipids bind in the active site and at the interfacial binding site (IBS); indeed, as a general rule the lipid interfaces of peripheral membrane proteins resist crystallographic determination. Here, however, we report X-ray crystal structures at 1.85 to 2.6 Å resolution of a venom toxin from the Chilean six-eyed sand spider Sicarius levii (terrosus) bound to a micelle-like agglomeration of product and substrate sphingolipids. Each enzyme subunit binds three sphingolipid molecules, one in the active site and two at adjacent noncatalytic sites, generating an interface that approximates the IBS predicted by molecular dynamics. The conformations of substrate and cyclic product in the active site definitively confirm our previously proposed catalytic mechanism. Comparisons with lipid-free structures show conformational changes in two loops that suggest a mechanism for allosteric/surface activation. Docking studies suggest that the variable preference of these toxins for phosphocholine and phosphoethanolamine head groups involves subtle changes in size and shape of the active-site pocket. The structures reveal key facets of the molecular basis of loxoscelism and show that in favorable cases crystallography can illuminate the IBS of peripheral membrane proteins.

  PublisherDOI

• Cientistas revelam o mecanismo mortal que o veneno de uma aranha usa para atacar as células humanas

  2026-04-08

  article1st authorCorresponding
  PublisherDOI

• Structure of phospholipase D BetaIB1i from Sicarius terrosus venom, H47N mutant bound to substrate sphingolipids at 2.60 A resolution

  2025-06-05 · 1 citations

  datasetSenior author
  PublisherDOI

• Protein salvage and repurposing in evolution: Phospholipase D toxins are stabilized by a remodeled scrap of a membrane association domain

  Protein Science · 2023 · 2 citations

  1st authorCorresponding
  • Chemistry
  • Computational biology
  • Biochemistry

  barrel fold of GDPD, while gaining a signature C-terminal expansion motif and losing a small insertion domain. Using sequence alignments and phylogenetic analysis, we infer that the C-terminal motif derives from a segment of an ancient bacterial PLAT domain. Formally, part of a protein containing a PLAT domain repeat underwent fusion to the C terminus of a GDPD barrel, leading to attachment of a segment of a PLAT domain, followed by a second complete PLAT domain. The complete domain was retained only in some basal homologs, but the PLAT segment was conserved and repurposed as the expansion motif. The PLAT segment corresponds to strands β7-β8 of a β-sandwich, while the expansion motif as represented in spider PLD toxins has been remodeled as an α-helix, a β-strand, and an ordered loop. The GDPD-PLAT fusion led to two acquisitions in founding the GDPD-like SMaseD/PLD family: (1) a PLAT domain that presumably supported early lipase activity by mediating membrane association, and (2) an expansion motif that putatively stabilized the catalytic domain, possibly compensating for, or permitting, loss of the insertion domain. Of wider significance, messy domain shuffling events can leave behind scraps of domains that can be salvaged, remodeled, and repurposed.

  PublisherOA PDFDOI

• Specificity of Loxosceles α clade phospholipase D enzymes for choline-containing lipids: Role of a conserved aromatic cage

  PLoS Computational Biology · 2022 · 12 citations

  • Biology
  • Biochemistry
  • Stereochemistry

  Spider venom GDPD-like phospholipases D (SicTox) have been identified to be one of the major toxins in recluse spider venom. They are divided into two major clades: the α clade and the β clade. Most α clade toxins present high activity against lipids with choline head groups such as sphingomyelin, while activities in β clade toxins vary and include preference for substrates containing ethanolamine headgroups (Sicarius terrosus, St_βIB1). A structural comparison of available structures of phospholipases D (PLDs) reveals a conserved aromatic cage in the α clade. To test the potential influence of the aromatic cage on membrane-lipid specificity we performed molecular dynamics (MD) simulations of the binding of several PLDs onto lipid bilayers containing choline headgroups; two SicTox from the α clade, Loxosceles intermedia αIA1 (Li_αIA) and Loxosceles laeta αIII1 (Ll_αIII1), and one from the β clade, St_βIB1. The simulation results reveal that the aromatic cage captures a choline-headgroup and suggest that the cage plays a major role in lipid specificity. We also simulated an engineered St_βIB1, where we introduced the aromatic cage, and this led to binding with choline-containing lipids. Moreover, a multiple sequence alignment revealed the conservation of the aromatic cage among the α clade PLDs. Here, we confirmed that the i-face of α and β clade PLDs is involved in their binding to choline and ethanolamine-containing bilayers, respectively. Furthermore, our results suggest a major role in choline lipid recognition of the aromatic cage of the α clade PLDs. The MD simulation results are supported by in vitro liposome binding assay experiments.

  PublisherDOI

• Churchill: Climate Change at the Arctic’s Edge

  ACS symposium series · 2021-06-15

  book-chapterSenior author

  In this chapter we survey the Arctic as a unified ecological web and observe how climate change imperils its ecological balance with consequences extending beyond the Arctic to our entire self-regulating Earth System.

  PublisherDOI

• Jimma: Bean to Brew—What’s Invested in a Cup of Coffee?

  ACS symposium series · 2021-06-15

  book-chapterSenior author

  ADVERTISEMENT RETURN TO BOOKPREVChapterNEXTJimma: Bean to Brew—What's Invested in a Cup of Coffee?Keith Peterman *Keith Peterman Chemistry Department, Kinsley School of Engineering, Sciences, and Technology, York College of Pennsylvania, York, Pennsylvania 17403, United States*Email: [email protected]More by Keith Peterman and Matthew CordesMatthew Cordes WritingWorks, Ltd., Lehighton, Pennsylvania 18235, United StatesMore by Matthew CordesDOI: 10.1021/bk-2021-1382.ch010Publication Date (Web):June 15, 2021Publication History Published online15 June 2021Request reuse permissions Copyright © 2021 American Chemical Society. Contextualizing Climate Change: Linking Science and CultureChapter 10pp 99-111ACS Symposium SeriesVol. 1382ISBN13: 9780841298354eISBN: 9780841298347Chapter Views37Citations-LEARN ABOUT THESE METRICSChapter Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Beverages,Pest control,Plant derived food,Plants,Sustainability Get e-Alerts

  PublisherDOI

• Switzerland: Glaciers Retreat

  ACS symposium series · 2021-06-15

  book-chapterSenior author

  ADVERTISEMENT RETURN TO BOOKPREVChapterNEXTSwitzerland: Glaciers RetreatKeith Peterman *Keith Peterman Chemistry Department, Kinsley School of Engineering, Sciences, and Technology, York College of Pennsylvania, York, Pennsylvania 17403, United States*Email: [email protected]More by Keith Peterman and Matthew CordesMatthew Cordes WritingWorks, Ltd., Lehighton, Pennsylvania 18235, United StatesMore by Matthew CordesDOI: 10.1021/bk-2021-1382.ch011Publication Date (Web):June 15, 2021Publication History Published online15 June 2021Request reuse permissions Copyright © 2021 American Chemical Society. Contextualizing Climate Change: Linking Science and CultureChapter 11pp 113-126ACS Symposium SeriesVol. 1382ISBN13: 9780841298354eISBN: 9780841298347Chapter Views31Citations-LEARN ABOUT THESE METRICSChapter Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Ablation,Climate,Climate change,Ice,Melting Get e-Alerts

  PublisherDOI

• Specificity of Loxosceles α Clade Phospholipase D Enzymes for Choline-Containing Lipids: Role of a Conserved Aromatic Cage

  Biophysical Journal · 2021-02-01

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• Collaborative Research: Head Group Preference in Recluse Spider Phospholipase D Toxins

  NSF · $405k · 2018–2023

• THE CONVERSION OF NONCODING SEQUENCES INTO PROTEINS

  NIH · $839k · 2013–2019

• CAREER: The Functional Evolution of Sequence-specific DNA-binding Proteins

  NSF · $698k · 2007–2013

• NIH Grant R01GM066806

  NIH · $2.5M · 2013

Frequent coauthors

• Greta J. Binford

  Lewis & Clark College

  19 shared

• Pamela A. Zobel-Thropp

  Lewis & Clark College

  9 shared

• Keith Peterman

  University of Pennsylvania

  9 shared

• Sue A. Roberts

  7 shared

• Vlad K. Kumirov

  University of Arizona

  7 shared

• Branwen M. Hall

  Massachusetts Institute of Technology

  6 shared

• Daniel M. Lajoie

  University of Arizona

  6 shared

• Robert T. Sauer

  Massachusetts Institute of Technology

  6 shared

Education

• Postdoc, Biology

  Massachusetts Institute of Technology

  2000

• Ph.D., Chemistry

  Yale University

  1994

• B.A., Chemistry/Romance Languages

  Bowdoin College

  1987