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Rational inhibitor design for Pseudomonas aeruginosa salicylate adenylation enzyme PchD

https://doi.org/10.1007/s00775-022-01941-8

Shelton, Catherine L.; Meneely, Kathleen M.; Ronnebaum, Trey A.; Chilton, Annemarie S.; Riley, Andrew P.; Prisinzano, Thomas E.; Lamb, Audrey L. (May 2022, JBIC Journal of Biological Inorganic Chemistry)

Abstract Pseudomonas aeruginosais an increasingly antibiotic-resistant pathogen that causes severe lung infections, burn wound infections, and diabetic foot infections.P. aeruginosaproduces the siderophore pyochelin through the use of a non-ribosomal peptide synthetase (NRPS) biosynthetic pathway. Targeting members of siderophore NRPS proteins is one avenue currently under investigation for the development of new antibiotics against antibiotic-resistant organisms. Here, the crystal structure of the pyochelin adenylation domain PchD is reported. The structure was solved to 2.11 Å when co-crystallized with the adenylation inhibitor 5′-O-(N-salicylsulfamoyl)adenosine (salicyl-AMS) and to 1.69 Å with a modified version of salicyl-AMS designed to target an active site cysteine (4-cyano-salicyl-AMS). In the structures, PchD adopts the adenylation conformation, similar to that reported for AB3403 fromAcinetobacter baumannii. Graphical abstract
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Kinetic and Structural Characterization of Trypanosoma cruzi Hypoxanthine–Guanine–Xanthine Phosphoribosyltransferases and Repurposing of Transition-State Analogue Inhibitors

https://doi.org/10.1021/acs.biochem.3c00116

Glockzin, Kayla; Meneely, Kathleen M.; Hughes, Ryan; Maatouk, Sean W.; Piña, Grace E.; Suthagar, Kajitha; Clinch, Keith; Buckler, Joshua N.; Lamb, Audrey L.; Tyler, Peter C.; et al (July 2023, Biochemistry)
Evidence for the Chemical Mechanism of RibB (3,4-Dihydroxy-2-butanone 4-phosphate Synthase) of Riboflavin Biosynthesis

https://doi.org/10.1021/jacs.2c03376

Kenjić, Nikola; Meneely, Kathleen M.; Wherritt, Daniel J.; Denler, Melissa C.; Jackson, Timothy A.; Moran, Graham R.; Lamb, Audrey L. (July 2022, Journal of the American Chemical Society)
Finding Ways to Relax: A Revisionistic Analysis of the Chemistry of E. coli GTP Cyclohydrolase II

https://doi.org/10.1021/acs.biochem.1c00511

Smith, Madison M.; Beaupre, Brett A.; Fourozesh, Dariush C.; Meneely, Kathleen M.; Lamb, Audrey L.; Moran, Graham R. (October 2021, Biochemistry)

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The 15-Amino Acid Repeat Region of Adenomatous Polyposis Coli Is Intrinsically Disordered and Retains Conformational Flexibility upon Binding β-Catenin

https://doi.org/10.1021/acs.biochem.0c00479

Rudeen, Aaron J.; Douglas, Justin T.; Xing, Minli; McDonald, W. Hayes; Lamb, Audrey L.; Neufeld, Kristi L. (October 2020, Biochemistry)
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What we've lost by closing our labs - and what we risk reopening them

Moran, Graham; Lamb, Audrey (June 2020, ASBMB today)

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