In some bacteria, cysteine is converted to cysteine sulfinic acid by cysteine dioxygenases (CDO) that are only ∼15–30% identical in sequence to mammalian CDOs. Among bacterial proteins having this range of sequence similarity to mammalian CDO are some that conserve an active site Arg residue (“Arg-type” enzymes) and some having...
Lactate monooxygenase (LMO) catalyzes the FMN-dependent "coupled" oxidation of lactate and O-2 to acetate, carbon dioxide, and water, involving pyruvate and hydrogen peroxide as enzyme-bound intermediates. Other alpha-hydroxy acid oxidase family members follow an "uncoupled pathway," wherein the alpha-keto acid product quickly dissociates before the reduced flavin reacts with oxygen....
The formation of hydrogen peroxide (H₂O₂) by the FAD-dependent α-glycerophosphate oxidase (GlpO), is important for the pathogenesis of Streptococcus pneumoniae and Mycoplasma pneumoniae. The structurally known GlpO from Streptococcus sp. (SspGlpO) is similar to the pneumococcal protein (SpGlpO) and provides a guide for drug design against that target. However, M....
Sulfur is one of the six elements required during the early stages of the evolution of life, and enzymes involved in sulfur transfer and oxidation are increasingly being recognized as potential drug targets for antimicrobials as well as for therapies for cancer, neurodegenerative and inflammatory diseases. Bacteria are able to...
The function of a protein is defined by its three-dimensional structure, and in understanding the three-dimensional structure of a protein, we gain an understanding of its function and mechanism. Protein structures, especially at high resolution, can provide detailed insights into many elements of enzyme function and catalysis – identifying residues...
The Fenna-Matthews-Olson antenna protein from the green bacterium Pelodictyon phaeum mediates the energy transfer from a peripheral antenna complex to the membrane-bound reaction center. The three-dimensional structure of this protein has been previously modeled using X-ray diffraction to a resolution limit of 2.0 Å, with R[subscript work] and R[subscript free]...
In this dissertation, I describe the experimental investigation of large superfluid helium droplets. The goal and direction of this thesis is to facilitate the use of these droplets as part of our project ss-EDI. The overall scheme of ss-EDI is to dope proteins inside helium droplets and collect a diffraction...
The planar peptide model has guided our understanding and interpretation of protein crystal structures since its origin in the 1950s. It is well understood that deviations from this model occur, but the majority of peptides are planar, as measured by the standard omega torsion angle. Here, we report the first...
Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank (PDB) archive,...
This thesis includes three studies involving different aspects of modeling protein structure. The first study illustrates the levels of insight available from atomic-resolution protein structures. The second study derives general trends of protein geometry from atomic-resolution structures and shows their implications for modeling. The third study creates a model of...