| 1. |
- Rodrigo-Unzueta, Ane, et al.
(författare)
-
Dissecting the Structural and Chemical Determinants of the “Open-to-Closed” Motion in the Mannosyltransferase PimA from Mycobacteria
- 2020
-
Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 59:32, s. 2934-2945
-
Tidskriftsartikel (refereegranskat)abstract
- The phosphatidyl-myo-inositol mannosyltransferase A (PimA) is an essential peripheral membrane glycosyltransferase that initiates the biosynthetic pathway of phosphatidyl-myo-inositol mannosides (PIMs), key structural elements and virulence factors of Mycobacterium tuberculosis. PimA undergoes functionally important conformational changes, including (i) α-helix-to-β-strand and β-strand-to-α-helix transitions and (ii) an “open-to-closed” motion between the two Rossmann-fold domains, a conformational change that is necessary to generate a catalytically competent active site. In previous work, we established that GDP-Man and GDP stabilize the enzyme and facilitate the switch to a more compact active state. To determine the structural contribution of the mannose ring in such an activation mechanism, we analyzed a series of chemical derivatives, including mannose phosphate (Man-P) and mannose pyrophosphate-ribose (Man-PP-RIB), and additional GDP derivatives, such as pyrophosphate ribose (PP-RIB) and GMP, by the combined use of X-ray crystallography, limited proteolysis, circular dichroism, isothermal titration calorimetry, and small angle X-ray scattering methods. Although the β-phosphate is present, we found that the mannose ring, covalently attached to neither phosphate (Man-P) nor PP-RIB (Man-PP-RIB), does promote the switch to the active compact form of the enzyme. Therefore, the nucleotide moiety of GDP-Man, and not the sugar ring, facilitates the “open-to-closed” motion, with the β-phosphate group providing the high-affinity binding to PimA. Altogether, the experimental data contribute to a better understanding of the structural determinants involved in the “open-to-closed” motion not only observed in PimA but also visualized and/or predicted in other glycosyltransfeases. In addition, the experimental data might prove to be useful for the discovery and/or development of PimA and/or glycosyltransferase inhibitors.
|
|
| 2. |
- Rodrigues, Camila, et al.
(författare)
-
Comparison of Intramuscular and Surface Electromyography Recordings towards the Control of Wearable Robots for Incomplete Spinal Cord Injury Rehabilitation
- 2020
-
Ingår i: Proceedings of the IEEE RAS and EMBS International Conference on Biomedical Robotics and Biomechatronics. - 2155-1774. ; 2020-November, s. 564-569
-
Konferensbidrag (refereegranskat)abstract
- Spinal Cord Injury (SCI) affects thousands of people worldwide every year. SCI patients have disrupted muscle recruitment and are more predisposed to other complications. To recover or enhance lower limbs functions, conventional rehabilitation programs are typically used. More recently, conventional programs have been combined with robot-assisted training. Electromyography (EMG) activity is generally used to record the electrical activity of the muscles, which in turn can be used to control robotic assistive devices as orthoses, prostheses and exoskeletons. In this sense, surface EMG can be used as input to myoelectric control but presents some limitations such as myoelectric crosstalk, as well as the influence of motion artefacts, and electromagnetic noise. EMG can also be recorded using intramuscular detection systems, which allows the detection of electric potentials closer to the muscle fibres and the recording of EMG activity from deeper muscles. This paper evaluates the quality of intramuscular EMG recordings compared to surface EMG signals, as a preliminary step to control EMG-driven exoskeletons. Seven healthy subjects performed submaximal knee and ankle flexion/extension movements with and without the use of a lower limb exoskeleton. Intramuscular recordings presented early muscle activation detecting times, which is a very important feature in real-time control, and good signal-to-noise ratio values, showing the potential of these biosignals as reliable input measures to control exoskeletons for rehabilitation purposes.
|
|
