A study on the flexibility of enzyme active sites

<p>Abstract</p> <p>Background</p> <p>A common assumption about enzyme active sites is that their structures are highly conserved to specifically distinguish between closely similar compounds. However, with the discovery of distinct enzymes with similar reaction chemistries, more and more studies discussing the structural flexibility of the active site have been conducted.</p> <p>Results</p> <p>Most of the existing works on the flexibility of active sites focuses on a set of pre-selected active sites that were already known to be flexible. This study, on the other hand, proposes an analysis framework composed of a new data collecting strategy, a local structure alignment tool and several physicochemical measures derived from the alignments. The method proposed to identify flexible active sites is highly automated and robust so that more extensive studies will be feasible in the future. The experimental results show the proposed method is (a) consistent with previous works based on manually identified flexible active sites and (b) capable of identifying potentially new flexible active sites.</p> <p>Conclusions</p> <p>This proposed analysis framework and the former analyses on flexibility have their own advantages and disadvantage, depending on the cause of the flexibility. In this regard, this study proposes an alternative that complements previous studies and helps to construct a more comprehensive view of the flexibility of enzyme active sites.</p

Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair.

Contrary to the long-held belief that DNA methylation of terminally differentiated cells is permanent and essentially immutable, post-mitotic neurons exhibit extensive DNA demethylation. The cellular function of active DNA demethylation in neurons, however, remains largely unknown. Tet family proteins oxidize 5-methylcytosine to initiate active DNA demethylation through the base-excision repair (BER) pathway. We found that synaptic activity bi-directionally regulates neuronal Tet3 expression. Functionally, knockdown of Tet or inhibition of BER in hippocampal neurons elevated excitatory glutamatergic synaptic transmission, whereas overexpressing Tet3 or Tet1 catalytic domain decreased it. Furthermore, dysregulation of Tet3 signaling prevented homeostatic synaptic plasticity. Mechanistically, Tet3 dictated neuronal surface GluR1 levels. RNA-seq analyses further revealed a pivotal role of Tet3 in regulating gene expression in response to global synaptic activity changes. Thus, Tet3 serves as a synaptic activity sensor to epigenetically regulate fundamental properties and meta-plasticity of neurons via active DNA demethylation

Protemot: prediction of protein binding sites with automatically extracted geometrical templates

Geometrical analysis of protein tertiary substructures has been an effective approach employed to predict protein binding sites. This article presents the Protemot web server that carries out prediction of protein binding sites based on the structural templates automatically extracted from the crystal structures of protein–ligand complexes in the PDB (Protein Data Bank). The automatic extraction mechanism is essential for creating and maintaining a comprehensive template library that timely accommodates to the new release of PDB as the number of entries continues to grow rapidly. The design of Protemot is also distinctive by the mechanism employed to expedite the analysis process that matches the tertiary substructures on the contour of the query protein with the templates in the library. This expediting mechanism is essential for providing reasonable response time to the user as the number of entries in the template library continues to grow rapidly due to rapid growth of the number of entries in PDB. This article also reports the experiments conducted to evaluate the prediction power delivered by the Protemot web server. Experimental results show that Protemot can deliver a superior prediction power than a web server based on a manually curated template library with insufficient quantity of entries. Availability:

Enumeration of spin-space groups: Towards a complete description of symmetries of magnetic orders

Symmetries of three-dimensional periodic scalar fields are described by 230 space groups (SGs). Symmetries of three-dimensional periodic (pseudo-) vector fields, however, are described by the spin-space groups (SSGs), which were initially used to describe the symmetries of magnetic orders. In SSGs, the real-space and spin degrees of freedom are unlocked in the sense that an operation could have different spacial and spin rotations. SSGs gives a complete symmetry description of magnetic structures, and have natural applications in the band theory of itinerary electrons in magnetically ordered systems with weak spin-orbit coupling.\textit{Altermagnetism}, a concept raised recently that belongs to the symmetry-compensated collinear magnetic orders but has non-relativistic spin splitting, is well described by SSGs. Due to the vast number and complicated group structures, SSGs have not yet been systematically enumerated. In this work, we exhaust SSGs based on the invariant subgroups of SGs, with spin operations constructed from three-dimensional (3D) real representations of the quotient groups for the invariant subgroups. For collinear and coplanar magnetic orders, the spin operations can be reduced into lower dimensional real representations. As the number of SSGs is infinite, we only consider SSGs that describe magnetic unit cells up to 12 times crystal unit cells. We obtain 157,289 non-coplanar, 24,788 coplanar-non-collinear, and 1,421 collinear SSGs. The enumerated SSGs are stored in an online database at \url{https://cmpdc.iphy.ac.cn/ssg} with a user-friendly interface. We also develop an algorithm to identify SSG for realistic materials and find SSGs for 1,626 magnetic materials. Our results serve as a solid starting point for further studies of symmetry and topology in magnetically ordered materials

VASP2KP: kp models and Lande g-factors from ab initio calculations

The $k\cdot p$ method is significant in condensed matter physics for the compact and analytical Hamiltonian. In the presence of magnetic field, it is described by the effective Zeeman's coupling Hamiltonian with Land\'e $g$-factors. Here, we develop an open-source package VASP2KP (including two parts: vasp2mat and mat2kp) to compute $k\cdot p$ parameters and Land\'e $g$-factors directly from the wavefunctions provided by the density functional theory (DFT) as implemented in Vienna ab initio Simulation Package (VASP). First, we develop a VASP patch vasp2mat to compute matrix representations of the generalized momentum operator $\mathbf{\hat{\pi}}=\mathbf{\hat{p}}+\frac{1}{2mc^2}\left(\mathbf{\hat{s}}\times\nabla V(\mathbf{r})\right)$, spin operator $\mathbf{\hat{s}}$, time reversal operator $\hat{T}$ and crystalline symmetry operators $\hat{R}$ on the DFT wavefunctions. Second, we develop a python code mat2kp to obtain the unitary transformation $U$ that rotates the degenerate DFT basis towards the standard basis, and then automatically compute the $k\cdot p$ parameters and $g$-factors. The theory and the methodology behind VASP2KP are described in detail. The matrix elements of the operators are derived comprehensively and computed correctly within the projector augmented wave method. We apply this package to some materials, e.g., Bi$_2$Se$_3$, Na$_3$Bi, Te, InAs and 1H-TMD monolayers. The obtained effective model's dispersions are in good agreement with the DFT data around the specific wave vector, and the $g$-factors are consistent with experimental data. The VASP2KP package is available at https://github.com/zjwang11/VASP2KP

Anomalous High-Energy Waterfall-Like Electronic Structure in 5 \u3cem\u3ed\u3c/em\u3e Transition Metal Oxide Sr\u3csub\u3e2\u3c/sub\u3eIrO\u3csub\u3e4\u3c/sub\u3e with a Strong Spin-Orbit Coupling

The low energy electronic structure of Sr2IrO4 has been well studied and understood in terms of an effective Jeff = 1/2 Mott insulator model. However, little work has been done in studying its high energy electronic behaviors. Here we report a new observation of the anomalous high energy electronic structure in Sr2IrO4. By taking high-resolution angle-resolved photoemission measurements on Sr2IrO4 over a wide energy range, we have revealed for the first time that the high energy electronic structures show unusual nearly-vertical bands that extend over a large energy range. Such anomalous high energy behaviors resemble the high energy waterfall features observed in the cuprate superconductors. While strong electron correlation plays an important role in producing high energy waterfall features in the cuprate superconductors, the revelation of the high energy anomalies in Sr2IrO4, which exhibits strong spin-orbit coupling and a moderate electron correlation, points to an unknown and novel route in generating exotic electronic excitations