Picture of Jon Clardy

Jon Clardy, Ph.D.

Christopher T. Walsh Professor of Biological Chemistry and Molecular Pharmacology

The laboratory focuses on biologically active small molecules, especially those from bacteria and fungi with an overall goal of understanding how small molecules control biological processes. 

Research:

The laboratory focuses on biologically active small molecules, especially those from bacteria and fungi with an overall goal of understanding how small molecules control biological processes.  Organizing themes include: 1) function-based discovery of microbially-produced small molecules and their roles in microbial symbioses , 2) function-based discovery of biologically active small molecules using high-throughput screening,  3) genome-based discovery of bacterially-produced small molecules. 

1.  We have focused on the small molecule exchanges that underlie multilateral symbioses involving bacteria, partly because they are widespread and poorly understood and partly because they lead to the discovery of new useful molecules in the biological context in which they evolved.  Current projects involve the bacterial symbionts of fungus-growing ants, members of the human gut microbiome linked to disease, and interactions between micro-algae and bacteria.

2.  We also continue to discover small molecules in a more medically relevant context: high-throughput screening for a variety of diseases.  In these projects we have focused on antibacterial, antifungal, and antiparasitic agents along with immunomodulators and anticancer agents. 

3.  It is now quite clear that well studied bacteria – the producers of drugs that are used on the ton scale, for example – are genetically capable of producing many more potentially useful small molecules.  The biosynthetic gene can be seen but the associated molecules have never been characterized.  Ways to access these cryptic metabolites is a current focus of the laboratory.

Address: 

Room C-643

240 Longwood Avenue

Boston, MA 02115

Publications View
The crystal structure of pyroglutamyl peptidase I from Bacillus amyloliquefaciens reveals a new structure for a cysteine protease.
Authors: Authors: Odagaki Y, Hayashi A, Okada K, Hirotsu K, Kabashima T, Ito K, Yoshimoto T, Tsuru D, Sato M, Clardy J.
Structure
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Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution.
Authors: Authors: Liang J, Choi J, Clardy J.
Acta Crystallogr D Biol Crystallogr
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Borrowing to make ends meet.
Authors: Authors: Clardy J.
Proc Natl Acad Sci U S A
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Crystallization and preliminary X-ray crystallographic analysis of the Pseudomonas aeruginosa cyclohexadienyl dehydratase.
Authors: Authors: Kongsaeree P, Liang J, Jensen RA, Clardy J.
Acta Crystallogr D Biol Crystallogr
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Discorhabdin P, a new enzyme inhibitor from a deep-water Caribbean sponge of the genus Batzella.
Authors: Authors: Gunasekera SP, McCarthy PJ, Longley RE, Pomponi SA, Wright AE, Lobkovsky E, Clardy J.
J Nat Prod
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Megathyrin B: a cytotoxic diterpene from Isodon megathyrsus.
Authors: Authors: Qiu SX, Sun HD, Lobkovsky E, Chai H, Clardy J, Farnsworth NR, Pezzuto JM, Fong HH.
Planta Med
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Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP.
Authors: Authors: Nassar N, Hoffman GR, Manor D, Clardy JC, Cerione RA.
Nat Struct Biol
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Structure of human methionine aminopeptidase-2 complexed with fumagillin.
Authors: Authors: Liu S, Widom J, Kemp CW, Crews CM, Clardy J.
Science
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Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products.
Authors: Authors: Handelsman J, Rondon MR, Brady SF, Clardy J, Goodman RM.
Chem Biol
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Thermodynamics of a transition state analogue inhibitor binding to Escherichia coli chorismate mutase: probing the charge state of an active site residue and its role in inhibitor binding and catalysis.
Authors: Authors: Lee AY, Zhang S, Kongsaeree P, Clardy J, Ganem B, Erickson JW, Xie D.
Biochemistry
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