• Publications
  • Influence
Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin.
Enzymatic targets for inhibitor design and therapeutic intervention are suggested by the similar ferric-ion ligation strategies used in the siderophores from Mycobacteria, Yersinia and E. coli pathogens. Expand
Crystal structure of Mycobacterium tuberculosis ClpP1P2 suggests a model for peptidase activation by AAA+ partner binding and substrate delivery
It is shown that cyclic acyldepsipeptides (ADEPs and agonist peptides synergistically activate ClpP1P2 by mimicking AAA+ partners and substrates, respectively, and determine the structure of the activated complex. Expand
Study of PcaV from Streptomyces coelicolor yields new insights into ligand-responsive MarR family transcription factors
This work describes how PcaV, a MarR family regulator in Streptomyces coelicolor, controls transcription of genes encoding β-ketoadipate pathway enzymes through its interaction with the pathway substrate, protocatechuate, and proposes that interaction of ligand with this arginine residue dictates conformational changes that modulate DNA binding. Expand
Genetic and Proteomic Analyses of Pupylation in Streptomyces coelicolor.
Cont constituents of the pupylome in Streptomyces coelicolor are defined for the first time and new evidence is presented that links pupylation and the oxidative stress response in this bacterium. Expand
The gene encoding RNase III in Streptomyces coelicolor is transcribed during exponential phase and is required for antibiotic production and for proper sporulation.
Phenotypic analysis of a constructed RNase III null mutant of Streptomyces coelicolor revealed that RNase III is required for both antibiotic production and proper formation of sporulation septa.Expand
A Retrograde Trafficking Inhibitor of Ricin and Shiga-Like Toxins Inhibits Infection of Cells by Human and Monkey Polyomaviruses
ABSTRACT Polyomaviruses are ubiquitous pathogens that cause severe disease in immunocompromised individuals. JC polyomavirus (JCPyV) is the causative agent of the fatal demyelinating diseaseExpand
Structural optimization of a retrograde trafficking inhibitor that protects cells from infections by human polyoma- and papillomaviruses.
These findings represent an advance in the development of drug candidates that can broadly protect humans from non-enveloped DNA viruses and toxins that exploit retrograde trafficking as a means for cell entry. Expand
Pairwise use of complexity-generating reactions in diversity-oriented organic synthesis.
Two pairs of complexity-generating reactions with an essential product-substrate relationship along a synthetic pathway are demonstrated, illustrating a key element in a planning algorithm for diversity-oriented synthesis. Expand
Diversity-oriented synthesis of cyclic acyldepsipeptides leads to the discovery of a potent antibacterial agent.
A novel route to the ADEP 4 peptidolactone core structure, featuring the Joullié-Ugi three-component reaction, was developed and used to prepare analogs that were designed using the principles of conformational analysis, which exhibited in vitro antibacterial activity against Enterococci that was fourfold higher than the parent compound. Expand
Restriction of the Conformational Dynamics of the Cyclic Acyldepsipeptide Antibiotics Improves Their Antibacterial Activity
It is shown that the rigidified ADEP analogs bind and activate ClpP at lower concentrations in vitro and have up to 1200-fold enhanced antibacterial activity when compared to those with the peptidolactone core structure common to two ADEP natural products. Expand