ABSTRACT
N-Acetyl-D-neuraminic acid lyase (NanA) catalyzes the breakdown of sialic acid (Neu5Ac) to N-acetyl-D-mannosamine (ManNAc) and pyruvate. NanA plays a key role in Neu5Ac catabolism in many pathogenic and bacterial commensals where sialic acid is available as a carbon and nitrogen source. Several pathogens or commensals decorate their surfaces with sialic acids as a strategy to escape host innate immunity. Catabolism of sialic acid is key to a range of host-pathogen interactions. In this study, atomic resolution structures of NanA from Fusobacterium nucleatum (FnNanA) in ligand-free and ligand-bound forms are reported at 2.32 and 1.76â Å resolution, respectively. F. nucleatum is a Gram-negative pathogen that causes gingival and periodontal diseases in human hosts. Like other bacterial N-acetylneuraminate lyases, FnNanA also shares the triosephosphate isomerase (TIM)-barrel fold. As observed in other homologous enzymes, FnNanA forms a tetramer. In order to characterize the structure-function relationship, the steady-state kinetic parameters of the enzyme are also reported.
Subject(s)
Fusobacterium nucleatum/enzymology , Oxo-Acid-Lyases/chemistry , Oxo-Acid-Lyases/metabolism , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Crystallography, X-Ray , Fusobacterium nucleatum/genetics , Hydrogen Bonding , Models, Molecular , N-Acetylneuraminic Acid/metabolism , Oxo-Acid-Lyases/genetics , Protein Conformation , Protein Folding , Pyruvic Acid/chemistry , Pyruvic Acid/metabolism , Schiff Bases/metabolism , Sequence Alignment , Tyrosine/chemistryABSTRACT
Diabetic neuropathies (DNs) are nerve-damaging disorders associated with diabetes. They are commonly attributed to peripheral nerves and primarily affect the limbs of the patient. They cause altered sensitivity to external stimuli along with loss in balance and reflexes of the affected patient. DNs are associated with a variety of clinical manifestations including autonomic failure and are caused by poor management of blood sugar levels. Imaging modalities provide vital information about early physiological changes in DNs. This review summarizes contributions by various teams of scientists in developing imaging methods to assess physiological changes in DNs and ongoing clinical trials where imaging modalities are applied to evaluate therapeutic intervention in DNs. Development of PET, single photon emission computed tomography, and magnetic resonance spectroscopy methods over the past 20 years are reviewed in the diagnostic assessment of DNs. Abnormal radiotracer pharmacokinetics and neurometabolite spectra in affected organs confirm physiological abnormalities in DN. With the use of the Siemens Biograph mMR and GE Signa - 60 cm (PET/MRI scanner), simultaneous acquisition of physiological and anatomical information could enhance understanding of DNs and accelerate drug development.
