Members of Dr. P. John Hart's lab use the tools of single
crystal X-ray diffraction, together with other biophysical and biochemical methods,
to characterize the structure and action of macromolecules involved in human
Current projects include the RNA lariat debranching enzyme (ALS), copper-zinc
superoxide dismutase (ALS), community acquired respiratory distress syndrome
(CARDS) toxin Mycoplasma pneumoniae
(asthma/ARDS); and matrix metalloproteinase-13 (osteoarthritis).
The lab is working on finding mechanisms
to combat schistosomiasis, a disease caused by parasitic blood flukes that
infect over 200 million people worldwide. Each project has a translational component,
and we work closely with the UTHSCSA Center
for Innovation in Drug Discovery in the structure-based pursuit of novel
Dr. Hart also serves as Director of the UTHSCSA X-ray Crystallography Core Labortatory (http://xray.uthscsa.edu).
Gleason JE, Galaleldeen A, Peterson RL, Taylor AB, Holloway SP, Waninger-Saroni J, Cormack BP, Cabelli DE, Hart PJ, Culotta VC. Candida albicans SOD5 represents the prototype of an unprecedented class of Cu-only superoxide dismutases required for pathogen defense. Proc Natl Acad Sci U S A. 2014 Apr 7.
Ivanova MI, Sievers SA, Guenther EL, Johnson LM, Winkler DD, Galaleldeen A, Sawaya MR, Hart PJ, Eisenberg DS. Aggregation-triggering segments of SOD1 fibril formation support a common pathway for familial and sporadic ALS. Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):197-201.
Valentim CL, Cioli D, Chevalier FD, Cao X, Taylor AB, Holloway SP,
Pica-Mattoccia L, Guidi A, Basso A, Tsai IJ, Berriman M,
Carvalho-Queiroz C, Almeida M, Aguilar H, Frantz DE, Hart PJ, LoVerde
PT, Anderson TJ. Genetic and molecular basis of drug resistance and species-specific drug action in schistosome parasites. Science. 2013 Dec 13;342(6164):1385-9.
Galaleldeen A, Taylor AB, Chen D, Schuermann JP, Holloway SP, Hou S, Gong S, Zhong G, Hart PJ. Structure of the Chlamydia trachomatis immunodominant antigen Pgp3. J Biol Chem. 2013 Jul 26;288(30):22068-79.
Seetharaman SV, Winkler DD, Taylor AB, Cao X, Whitson LJ, Doucette PA,
Valentine JS, Schirf V, Demeler B, Carroll MC, Culotta VC, Hart PJ. Disrupted zinc-binding sites in structures of pathogenic SOD1 variants D124V and H80R. Biochemistry. 2010 Jul 13;49(27):5714-25.