Role of PheE15 gate in ligand entry and nitric oxide detoxification function of Mycobacterium tuberculosis truncated hemoglobin N

The truncated hemoglobin N, HbN, of Mycobacterium tuberculosis is endowed with a potent nitric oxide dioxygenase (NOD) activity that allows it to relieve nitrosative stress and enhance in vivo survival of its host. Despite its small size, the protein matrix of HbN hosts a two-branched tunnel, consisting of orthogonal short and long channels, that connects the heme active site to the protein surface. A novel dual-path mechanism has been suggested to drive migration of O(2) and NO to the distal heme cavity. While oxygen migrates mainly by the short path, a ligand-induced conformational change regulates opening of the long tunnel branch for NO, via a phenylalanine (PheE15) residue that acts as a gate. Site-directed mutagenesis and molecular simulations have been used to examine the gating role played by PheE15 in modulating the NOD function of HbN. Mutants carrying replacement of PheE15 with alanine, isoleucine, tyrosine and tryptophan have similar O(2)/CO association kinetics, but display significant reduction in their NOD function. Molecular simulations substantiated that mutation at the PheE15 gate confers significant changes in the long tunnel, and therefore may affect the migration of ligands. These results support the pivotal role of PheE15 gate in modulating the diffusion of NO via the long tunnel branch in the oxygenated protein, and hence the NOD function of HbN

Using permeable membranes to produce hydrogen and oxygen from water

Concept may make it profitable to obtain hydrogen fuel from water. Laboratory tests have demonstrated that method enables decomposition of water several orders of magnitude beyond equilibrium state where only small amounts of free hydrogen are present

Toward fault-tolerant quantum computation without concatenation

It has been known that quantum error correction via concatenated codes can be done with exponentially small failure rate if the error rate for physical qubits is below a certain accuracy threshold. Other, unconcatenated codes with their own attractive features-improved accuracy threshold, local operations-have also been studied. By iteratively distilling a certain two-qubit entangled state it is shown how to perform an encoded Toffoli gate, important for universal computation, on CSS codes that are either unconcatenated or, for a range of very large block sizes, singly concatenated.Comment: 12 pages, 2 figures, replaced: new stuff on error models, numerical example for concatenation criteri

Building and exhibition layout: Sainsbury Wing compared with Castelvecchio

It has always been thought that there are two dimensions in museum experience: the experience of space which can be distinguished from that of exhibits, as the former is largely non-discursive while the latter is more in the discursive domain. This paper aims to contribute to the description and understanding of the intricate pattern of interdependencies between the two parameters of the microstructure of the gallery space, the design of space and of the display layout. The paper uses rigorous methods of ‘spatial data’ collection and analysis (analytic representations of spatial relationships, and systematic representations of the movement pattern) and on this objective foundation builds an interpretative and critical argument

THE MEASUREMENT OF HIGH-SPEED RAILWAY (HSR)-PRECISION ENGINEERING

The paper proposed the optimization of the network construction timing of the control network according to the specific conditions of the survey route. Moreover, presented here are the adjustments according to the layout requirements of the control network layout process, strengthening the control of the line level base point during the construction process. Several optimization solutions are discussed for the special design of the level control before the construction of the long tunnel. It has been explained the methodology to introduce new Continuously Operating Reference Station (CORS) technology in railway survey and design with appropriately adjustment of the position requirements of the control network according to the specification. In order to carry out the special design of the levelling route with precision, it is advisable to set a certain stable reference point in the level control of the long line. The proposed methodology can effectively solve some problems existing in the current high-speed railway construction process, and make the precision measurement control network better for survey, design, construction, supervision and operation

Endogenous agonist–bound S1PR3 structure reveals determinants of G protein–subtype bias

脂質受容体の新たな活性化機構を解明 --脂質がまっすぐ伸びて活性化--. 京都大学プレスリリース. 2021-06-10.Sphingosine-1-phosphate (S1P) regulates numerous important physiological functions, including immune response and vascular integrity, via its cognate receptors (S1PR1 to S1PR5); however, it remains unclear how S1P activates S1PRs upon binding. Here, we determined the crystal structure of the active human S1PR3 in complex with its natural agonist S1P at 3.2-Å resolution. S1P exhibits an unbent conformation in the long tunnel, which penetrates through the receptor obliquely. Compared with the inactive S1PR1 structure, four residues surrounding the alkyl tail of S1P (the “quartet core”) exhibit orchestrating rotamer changes that accommodate the moiety, thereby inducing an active conformation. In addition, we reveal that the quartet core determines G protein selectivity of S1PR3. These results offer insight into the structural basis of activation and biased signaling in G protein–coupled receptors and will help the design of biased ligands for optimized therapeutics