Rebooting a sports pharmacy advanced pharmacy practice experience: Utilizing medicinal chemistry as a foundational approach to get pharmacists back in the game.

Background And Purpose: To implement a sports pharmacy advanced pharmacy practice experience (SP-APPE) utilizing medicinal chemistry as a foundational approach.

Educational Activity And Setting: A student-pharmacist and medicinal chemistry faculty member collaborated to reboot a SP-APPE. Approached from a medicinal chemistry perspective and tailored to the infrastructure of the university, three fourth-year student-pharmacists piloted the SP-APPE (fall 2017 to fall 2018).

A multiyear comparison of flipped- vs. lecture-based teaching on student success in a pharmaceutical science class.

Background And Purpose: To gauge the potential effect of mode of content delivery on overall student success in a pharmaceutical sciences course in a doctor of pharmacy program.

Educational Activity And Setting: Principles of Drug Action I (PDAI) is a first-year pharmaceutical science course typically taught by multiple faculty, and each utilizes their own approach to deliver course content. Over a seven year period, the course naturally separated into blocks.

A pharmacy student's role as a teaching assistant in an undergraduate medicinal chemistry course - Implementation, evaluation, and unexpected opportunities for educational outreach.

Background And Purpose: To describe 1) a pharmacy student's teaching assistant (TA) role in an undergraduate medicinal chemistry course, 2) an active learning module co-developed by the TA and instructor, and 3) the unexpected opportunities for pharmacy educational outreach that resulted from this collaboration.

Educational Activity And Setting: Medicinal Chemistry (CHM3413) is an undergraduate course offered each fall at Palm Beach Atlantic University (PBA). As a TA for CHM3413, a pharmacy student from the Gregory School of Pharmacy (GSOP) at PBA co-developed and implemented an active learning module emphasizing foundational medicinal chemistry concepts as they pertain to performance enhancing drugs (PEDs).

Cooperative damage recognition by UvrA and UvrB: identification of UvrA residues that mediate DNA binding.

Nucleotide excision repair (NER) is responsible for the recognition and removal of numerous structurally unrelated DNA lesions. In prokaryotes, the proteins UvrA, UvrB and UvrC orchestrate the recognition and excision of aberrant lesions from DNA. Despite the progress we have made in understanding the NER pathway, it remains unclear how the UvrA dimer interacts with DNA to facilitate DNA damage recognition.

NMR analysis of [methyl-13C]methionine UvrB from Bacillus caldotenax reveals UvrB-domain 4 heterodimer formation in solution.

UvrB is a central DNA damage recognition protein involved in bacterial nucleotide excision repair. Structural information has been limited by the apparent disorder of the C-terminal domain 4 in crystal structures of intact UvrB; in solution, the isolated domain 4 is found to form a helix-loop-helix dimer. In order to gain insight into the behavior of UvrB in solution, we have performed NMR studies on [methyl-13C]methionine-labeled UvrB from Bacillus caldotenax (molecular mass=75 kDa).

The C-terminal zinc finger of UvrA does not bind DNA directly but regulates damage-specific DNA binding.

In prokaryotic nucleotide excision repair, UvrA recognizes DNA perturbations and recruits UvrB for the recognition and processing steps in the reaction. One of the most remarkable aspects of UvrA is that it can recognize a wide range of DNA lesions that differ in chemistry and structure. However, how UvrA interacts with DNA is unknown.

UvrB domain 4, an autoinhibitory gate for regulation of DNA binding and ATPase activity.

UvrB, a central DNA damage recognition protein in bacterial nucleotide excision repair, has weak affinity for DNA, and its ATPase activity is activated by UvrA and damaged DNA. Regulation of DNA binding and ATP hydrolysis by UvrB is poorly understood. Using atomic force microscopy and biochemical assays, we found that truncation of domain 4 of Bacillus caldotenax UvrB (UvrBDelta4) leads to multiple changes in protein function.

Structural basis for DNA recognition and processing by UvrB.

DNA-damage recognition in the nucleotide excision repair (NER) cascade is a complex process, operating on a wide variety of damages. UvrB is the central component in prokaryotic NER, directly involved in DNA-damage recognition and guiding the DNA through repair synthesis. We report the first structure of a UvrB-double-stranded DNA complex, providing insights into the mechanism by which UvrB binds DNA, leading to formation of the preincision complex.

'Close-fitting sleeves': DNA damage recognition by the UvrABC nuclease system.

DNA damage recognition represents a long-standing problem in the field of protein-DNA interactions. This article reviews our current knowledge of how damage recognition is achieved in bacterial nucleotide excision repair through the concerted action of the UvrA, UvrB, and UvrC proteins.

Structural insights into the first incision reaction during nucleotide excision repair.

Nucleotide excision repair is a highly conserved DNA repair mechanism present in all kingdoms of life. The incision reaction is a critical step for damage removal and is accomplished by the UvrC protein in eubacteria. No structural information is so far available for the 3' incision reaction.

Identification of residues within UvrB that are important for efficient DNA binding and damage processing.

The UvrB protein is the central recognition protein in bacterial nucleotide excision repair. We have shown previously that the highly conserved beta-hairpin motif in Bacillus caldotenax UvrB is essential for DNA binding, damage recognition, and UvrC-mediated incision, as deletion of the upper part of the beta-hairpin (residues 97-112) results in the inability of UvrB to be loaded onto damaged DNA, defective incision, and the lack of strand-destabilizing activity. In this work, we have further examined the role of the beta-hairpin motif of UvrB by a mutational analysis of 13 amino acids within or in the vicinity of the beta-hairpin.

Analyzing the handoff of DNA from UvrA to UvrB utilizing DNA-protein photoaffinity labeling.

To better define the molecular architecture of nucleotide excision repair intermediates it is necessary to identify the specific domains of UvrA, UvrB, and UvrC that are in close proximity to DNA damage during the repair process. One key step of nucleotide excision repair that is poorly understood is the transfer of damaged DNA from UvrA to UvrB, prior to incision by UvrC. To study this transfer, we have utilized two types of arylazido-modified photoaffinity reagents that probe residues in the Uvr proteins that are closest to either the damaged or non-damaged strands.

Interactions between UvrA and UvrB: the role of UvrB's domain 2 in nucleotide excision repair.

Nucleotide excision repair (NER) is a highly conserved DNA repair mechanism present in all kingdoms of life. UvrB is a central component of the bacterial NER system, participating in damage recognition, strand excision and repair synthesis. None of the three presently available crystal structures of UvrB has defined the structure of domain 2, which is critical for the interaction with UvrA.