Mechanisms of Action Anticipation in Table Tennis Players: A Multivoxel Pattern Analysis Study.

An exceptional ability to accurately anticipate an opponent's action is paramount for competitive athletes and highlights their experiential mastery. Despite conventional associations of action observation with specific brain regions, neuroimaging discrepancies persist. To explore the brain regions and neural mechanisms undergirding action anticipation, we compared distinct brain activation patterns involved in table tennis serve anticipation of expert table tennis athletes vs. non-experts by using both univariate analysis and multivoxel pattern analysis (MVPA). We collected functional magnetic resonance imaging data from 29 table tennis experts and 34 non-experts as they pressed a button to predict the trajectory of a ball in a table tennis serve video truncated at the moment of racket-ball contact vs. pressing any button while viewing a static image of the first video frame. MVPA was applied to assess whether it could accurately differentiate experts from non-experts. MVPA results indicated moderate accuracy (90.48%) for differentiating experts from non-experts. Brain regions contributing most to the differentiation included the left cerebellum, the vermis, the right middle temporal pole, the inferior parietal cortex, the bilateral paracentral lobule, and the left supplementary motor area. The findings suggest that brain regions associated with cognitive conflict monitoring and motor cognition contribute to the action anticipation ability of expert table tennis players.

Motor experience modulates neural processing of lexical action language: Evidence from rugby players.

The perceptual symbol theory proposes a sensorimotor simulation in language processing, emphasizing the role of motor experience. However, the neural basis of motor experience on lexical-level language processing remains little known. In the current fMRI study, we compared brain activation and task-based functional connectivity in 28 rugby players and 28 novices during rugby- specialized and daily verb processing. Distinct differences were observed between the two groups in the bilateral superior temporal gyrus and left angular gyrus regions during specialized verb processing. Notably, intergroup functional connectivity was evident between the left superior temporal gyrus and the right precentral gyrus during specialized verb processing. This study contributes insights into the neural responses and connectivity patterns associated with motor experience at the lexical level, highlighting its potential impact on language processing.

Crystal Structure of Aldehyde Dehydrogenase 16 Reveals Trans-Hierarchical Structural Similarity and a New Dimer.

The aldehyde dehydrogenase (ALDH) superfamily is a vast group of enzymes that catalyze the NAD+-dependent oxidation of aldehydes to carboxylic acids. ALDH16 is perhaps the most enigmatic member of the superfamily, owing to its extra C-terminal domain of unknown function and the absence of the essential catalytic cysteine residue in certain non-bacterial ALDH16 sequences. Herein we report the first production of recombinant ALDH16, the first biochemical characterization of ALDH16, and the first crystal structure of ALDH16. Recombinant expression systems were generated for the bacterial ALDH16 from Loktanella sp. and human ALDH16A1. Four high-resolution crystal structures of Loktanella ALDH16 were determined. Loktanella ALDH16 is found to be a bona fide enzyme, exhibiting NAD+-binding, ALDH activity, and esterase activity. In contrast, human ALDH16A1 apparently lacks measurable aldehyde oxidation activity, suggesting that it is a pseudoenzyme, consistent with the absence of the catalytic Cys in its sequence. The fold of ALDH16 comprises three domains: NAD+-binding, catalytic, and C-terminal. The latter is unique to ALDH16 and features a Rossmann fold connected to a protruding ß-flap. The tertiary structural interactions of the C-terminal domain mimic the quaternary structural interactions of the classic ALDH superfamily dimer, a phenomenon we call "trans-hierarchical structural similarity." ALDH16 forms a unique dimer in solution, which mimics the classic ALDH superfamily dimer-of-dimer tetramer. Small-angle X-ray scattering shows that human ALDH16A1 has the same dimeric structure and fold as Loktanella ALDH16. We suggest that the Loktanella ALDH16 structure may be considered to be the archetype of the ALDH16 family.

Structural Evidence for Rifampicin Monooxygenase Inactivating Rifampicin by Cleaving Its Ansa-Bridge.

Rifampicin monooxygenase (RIFMO) decreases the potency of rifampicin (RIF) by converting it to oxidative products. Further decomposition of RIF has been observed in bacteria producing RIFMO and contributes to RIFMO-mediated drug resistance. Here we report the first crystal structure of RIFMO in complex with the hydroxylated RIF product. The 2.10 Å resolution structure reveals a breach of the ansa aliphatic chain of RIF between naphthoquinone C2 and amide N1. Our data suggest that RIFMO catalyzes the hydroxylation of RIF at the C2 atom followed by cleavage of the ansa linkage, which leads to inactivation of the antibiotic by preventing key contacts with the RNA polymerase target.

Structure, function, and mechanism of proline utilization A (PutA).

Proline has important roles in multiple biological processes such as cellular bioenergetics, cell growth, oxidative and osmotic stress response, protein folding and stability, and redox signaling. The proline catabolic pathway, which forms glutamate, enables organisms to utilize proline as a carbon, nitrogen, and energy source. FAD-dependent proline dehydrogenase (PRODH) and NAD+-dependent glutamate semialdehyde dehydrogenase (GSALDH) convert proline to glutamate in two sequential oxidative steps. Depletion of PRODH and GSALDH in humans leads to hyperprolinemia, which is associated with mental disorders such as schizophrenia. Also, some pathogens require proline catabolism for virulence. A unique aspect of proline catabolism is the multifunctional proline utilization A (PutA) enzyme found in Gram-negative bacteria. PutA is a large (>1000 residues) bifunctional enzyme that combines PRODH and GSALDH activities into one polypeptide chain. In addition, some PutAs function as a DNA-binding transcriptional repressor of proline utilization genes. This review describes several attributes of PutA that make it a remarkable flavoenzyme: (1) diversity of oligomeric state and quaternary structure; (2) substrate channeling and enzyme hysteresis; (3) DNA-binding activity and transcriptional repressor function; and (4) flavin redox dependent changes in subcellular location and function in response to proline (functional switching).

The Structure of the Antibiotic Deactivating, N-hydroxylating Rifampicin Monooxygenase.

Rifampicin monooxygenase (RIFMO) catalyzes the N-hydroxylation of the natural product antibiotic rifampicin (RIF) to 2'-N-hydroxy-4-oxo-rifampicin, a metabolite with much lower antimicrobial activity. RIFMO shares moderate sequence similarity with well characterized flavoprotein monooxygenases, but the protein has not been isolated and characterized at the molecular level. Herein, we report crystal structures of RIFMO from Nocardia farcinica, the determination of the oligomeric state in solution with small angle x-ray scattering, and the spectrophotometric characterization of substrate binding. The structure identifies RIFMO as a class A flavoprotein monooxygenase and is similar in fold and quaternary structure to MtmOIV and OxyS, which are enzymes in the mithramycin and oxytetracycline biosynthetic pathways, respectively. RIFMO is distinguished from other class A flavoprotein monooxygenases by its unique middle domain, which is involved in binding RIF. Small angle x-ray scattering analysis shows that RIFMO dimerizes via the FAD-binding domain to form a bell-shaped homodimer in solution with a maximal dimension of 110 Å. RIF binding was monitored using absorbance at 525 nm to determine a dissociation constant of 13 µm Steady-state oxygen consumption assays show that NADPH efficiently reduces the FAD only when RIF is present, implying that RIF binds before NADPH in the catalytic scheme. The 1.8 Å resolution structure of RIFMO complexed with RIF represents the precatalytic conformation that occurs before formation of the ternary E-RIF-NADPH complex. The RIF naphthoquinone blocks access to the FAD N5 atom, implying that large conformational changes are required for NADPH to reduce the FAD. A model for these conformational changes is proposed.

High-resolution crystal structures of alternate forms of the human CD44 hyaluronan-binding domain reveal a site for protein interaction.

Two new crystal structures of the extracellular hyaluronan-binding domain of human CD44 are described at high resolution. A hexagonal crystal form at 1.60 Šresolution and a monoclinic form at 1.08 Šresolution both have two molecules in the asymmetric unit arranged about a similar noncrystallographic twofold axis of symmetry. These structures are compared with those previously reported at 2.20 Šresolution to show that the fold is quite resistant to structural deformation in different crystal environments. Unexpectedly, a short peptide is found in the monoclinic crystals at a site remote from the known hyaluronan-binding groove. The peptide with a valine at the carboxy-terminus must have co-purified from the bacterial expression host and binds on the opposite side of the domain from the known hyaluronan-binding groove. This opportunistic binding may identify a site of interaction used as CD44 assembles with other proteins to accomplish effective signaling regarding changes to the extracellular environment.

Fragment-based identification of an inducible binding site on cell surface receptor CD44 for the design of protein-carbohydrate interaction inhibitors.

Selective inhibitors of hyaluronan (HA) binding to the cell surface receptor CD44 will have value as probes of CD44-mediated signaling and have potential as therapeutic agents in chronic inflammation, cardiovascular disease, and cancer. Using biophysical binding assays, fragment screening, and crystallographic characterization of complexes with the CD44 HA binding domain, we have discovered an inducible pocket adjacent to the HA binding groove into which small molecules may bind. Iterations of fragment combination and structure-driven design have allowed identification of a series of 1,2,3,4-tetrahydroisoquinolines as the first nonglycosidic inhibitors of the CD44-HA interaction. The affinity of these molecules for the CD44 HA binding domain parallels their ability to interfere with CD44 binding to polymeric HA in vitro. X-ray crystallographic complexes of lead compounds are described and compared to a new complex with a short HA tetrasaccharide, to establish the tetrahydroisoquinoline pharmacophore as an attractive starting point for lead optimization.

Silver nanoparticles assemblies mediated by functionalized biomimetic oligomers.

The interaction between biopolymers and metal nanoparticles (AgNPs) is a key element in the development of biomimetic nanomaterials with applications in catalysis, delivery, and recognition. Here we report a facile method for the functionalization of AgNPs by N-substituted glycine oligomers, "peptoids." Based on the established affinity between phenanthroline ligand and Ag(0), we synthesized a peptoid bearing 1,10-phenanthroline at the N-terminus (PHP). Treatment of AgNPs that were pre-stabilized by citrate ions, with PHP, leads to the formation of aggregates as suggested by UV-vis spectroscopy. Transmission electron microscopy (TEM) revealed that the replacement of citrate ions by PHP yields spherical assemblies of AgNPs. These peptoids/AgNPs hybrids, as well as the ability of functional biomimetic oligomers to mediate the assembly of metal nanoparticles, hold potential for applications in sensor materials, biology, and catalysis.