The C-terminal Region of D-DT Regulates Molecular Recognition for Protein-Ligand Complexes.

Systematic analysis of molecular recognition is critical for understanding the biological function of macromolecules. For the immunomodulatory protein D-dopachrome tautomerase (D-DT), the mechanism of protein-ligand interactions is poorly understood. Here, 17 carefully designed protein variants and wild type (WT) D-DT were interrogated with an array of complementary techniques to elucidate the structural basis of ligand recognition. Utilization of a substrate and two selective inhibitors with distinct binding profiles offered previously unseen mechanistic insights into D-DT-ligand interactions. Our results demonstrate that the C-terminal region serves a key role in molecular recognition via regulation of the active site opening, protein-ligand interactions, and conformational flexibility of the pocket's environment. While our study is the first comprehensive analysis of molecular recognition for D-DT, the findings reported herein promote the understanding of protein functionality and enable the design of new structure-based drug discovery projects.

Concurrent COVID-19 and pneumocystis carinii pneumonia in a patient subsequently found to have underlying hairy cell leukemia.

SARS-CoV-2 infection manifestation has great diversity and it becomes even greater while co-infection occurs or there is a serious underlying disease in an affected patient. In this case report, we present a case of a 71-year-old man who underwent a chest CT scan following the development of fever, weakness, and pulmonary symptoms. Chest CT scan showed segmental consolidation with centrilobular nodular infiltration, ground glass opacifications in the inferior segment of the left upper and lower lobes, and left lung pleural thickening which was atypical for either COVID-19 infection or pneumocystis carinii pneumonia but his SARS-CoV-2 PCR result was positive and he received COVID-19 treatment. His symptoms recurred after a few months with the same chest CT findings and subsequent bronchoalveolar lavage revealed the presence of pneumocystis carinii infection. Consequently, he received cotrimoxazole which caused improvement in symptoms, nonetheless splenomegaly and anemia remained in his clinical and laboratory investigation. Accordingly, bone marrow study and flow cytometry was done and confirmed the previously undiagnosed hairy cell leukemia. This case accentuates the fact that when we face atypical clinical or paraclinical features in a COVID-19 patient, we should explore for coinfection or unknown underlying diseases.