Characteristics of precipitation changes during tropical cyclone processes in China from 1980 to 2019.

Tropical cyclones (TCs) and their associated intense rainfall are among the most significant natural disasters. Exploring the characteristics of tropical cyclone precipitation (TCP) has always been a challenging issue in TC research. This study utilized the TC track data from the International Best Track Archive for Climate Stewardship and precipitation data from the multi-source weighted-ensemble precipitation covering the years 1980-2019, to examine shifts in precipitation rates and peak precipitation levels before and after TC landfall. The results highlight several key findings: (1) Precipitation during the TC landfall process is relatively stable beforehand but tends to decrease slightly after landfall. Generally, the maximum precipitation occurs during the landfall. (2) From 1980 to 2019, the rate of precipitation changes before landfall has significantly increased. Conversely, after the year 2000, the rate of precipitation changes after landfall has significantly decreased. (3) Over the past 40 years, while peak precipitation levels of landfalling TCs have remained relatively constant, the total precipitation has shown an increasing trend, particularly in regions like the main island of Hainan, southern Zhejiang, and Shanghai, which are characterized by high peak precipitation. The results help clarify the TC processes and provide reference points for parameter selection in regional TCP modeling.

The effect of cold therapy combined with ERAS in the postoperative care of patients undergoing total knee arthroplasty.

OBJECTIVE: To investigate the nursing effect of cold therapy combined with enhanced recovery after surgery (ERAS) in patients undergoing total knee arthroplasty (TKA). METHODS: Eighty patients with knee osteoarthritis who underwent TKA in our hospital from August 2020 to January 2021 were enrolled in this study, and they were divided into a control group (n=40) and a study group (n=40) according to the nursing procedures. The time and cost of rehabilitation, pain level, recovery of knee function, incidence of postoperative complications, self-care ability, quality of life, and nursing satisfaction were compared between the two groups. RESULTS: The time of rehabilitation and time to out-of-bed activities in the study group were significantly shorter than those in the control group (P < 0.05), and the cost of rehabilitation in the study group was significantly lower than that in the control group (P < 0.05). There was no significant difference in preoperative visual analogue scale (VAS) scores (at rest, during exercise) between the two groups (P > 0.05). These scores in the study group were significantly lower than those in the control group at 6 h, 24 h, 48 h, and 72 h postoperatively (P < 0.05). The preoperative Hospital for Special Surgery (HSS), range of motion (ROM) and Barthel scores did not differ significantly between the two groups (P > 0.05). The postoperative ROM and Barthel scores were decreased to the lowest at 3 d postoperatively and gradually increased with time, and the HSS, ROM and Barthel scores in the study group were significantly higher than those in the control group (P < 0.05). The incidence of postoperative complications in the study group was significantly lower than those in the control group, and overall nursing satisfaction in the study group was significantly higher than those in the control group (P < 0.05). After discharge, the SF-36 scores of patients in both groups were higher than those before surgery, and the SF-36 scores in the study group were significantly higher than those in the control group (P < 0.05). CONCLUSION: The cold therapy combined with ERAS for patients undergoing TKA can improve the postoperative swelling and pain of the affected limb, inspire patients' autonomy in postoperative rehabilitation training, shorten the time to out-of-bed activity, prevent patients from developing venous thrombosis, promote recovery of knee function, and improve patients' postoperative self-care ability and quality of life.

Crystal structure of the polyketide cyclase from Mycobacterium tuberculosis.

About 40% of proteins are classified as conserved hypothetical proteins in Mycobacterium tuberculosis (TB). Identification and characterization of these proteins are beneficial to understand the pathogenesis of TB and exploiting novel drugs for TB treatments. The polyketide cyclase, a protein from M. tuberculosis ( MtPC) has been annotated as a hypothetical protein in Uniprot database. Sequence analysis shows that the MtPC belongs to the NTF2-like superfamily proteins with diverse functions. Here, we determined the crystal structure of MtPC at a resolution of 2.4 Šand measured backbone relaxation parameters for the MtPC protein. MtPC exists as a dimer in solution, and each subunit contains a six-stranded mixed ß-sheet and three α helixes which are arranged in the order α1-α2-ß1-ß2-α3-ß3-ß4-ß5-ß6. The NMR dynamics analysis showed that the overall structure of MtPC is highly rigid on ps-ns time scales. Furthermore, we predicted the potential function of MtPC based on the crystal structure. Our results lay the basis for further exploiting and mechanistically understanding the biological functions of MtPC.

1H, 13C, 15N backbone and side-chain chemical shift assignments of the polyketide cyclase from Mycobacterium tuberculosis.

Polyketide cyclase from Mycobacterium tuberculosis (MtPC) is related to the formation of sterol derivatives, which may play a role in immune escape in the initial stage of macrophage infection by Mycobacterium tuberculosis. However, the structure and specific functions of MtPC are still unknown. Here we report the backbone and side-chain NMR resonance assignments for the MtPC. Most resonances were assigned and the secondary structure was predicted according to the assigned backbone resonances by TALOS-N and PECAN. These NMR assignments represent a first step towards researching the structure and function of MtPC.

Structure and folding of four putative kink turns identified in structured RNA species in a test of structural prediction rules.

k-Turns are widespread key architectural elements that occur in many classes of RNA molecules. We have shown previously that their folding properties (whether or not they fold into their tightly kinked structure on addition of metal ions) and conformation depend on their local sequence, and we have elucidated a series of rules for prediction of these properties from sequence. In this work, we have expanded the rules for prediction of folding properties, and then applied the full set to predict the folding and conformation of four probable k-turns we have identified amongst 224 structured RNA species found in bacterial intergenenic regions by the Breaker lab (1). We have analyzed the ion-dependence of folding of the four k-turns using fluorescence resonance energy transfer, and determined the conformation of two of them using X-ray crystallography. We find that the experimental data fully conform to both the predicted folding and conformational properties. We conclude that our folding rules are robust, and can be applied to new k-turns of unknown characteristics with confidence.

1H, 13C, 15N backbone and side-chain resonance assignments of the pathogenic G131V mutant of human prion protein (91-231).

Human prion disease, also known as transmissible spongiform encephalopathy (TSEs), is caused by the conformational conversion of the normal cellular prion protein (PrPC) into the scrapie form (PrPSc). Pathogenic point mutations of prion proteins typically facilitate conformational conversion and lead to inherited prion diseases. A previous study has demonstrated that the pathogenic G131V mutation of human prion protein (HuPrP) brings in Gerstmann-Sträussler-Scheinker syndrome. However, the three-dimensional structure and dynamic features of the HuPrP(G131V) mutant remain unclear. It is expected that the determination of these structural bases will be beneficial to the pathogenic mechanistic understanding of G131V-related prion diseases. Here, we performed 1H, 15N, 13C backbone and side-chain resonance assignments of the G131V mutant of HuPrP(91-231) by using heteronuclear multi-dimensional NMR spectroscopy, and predicted the secondary structural elements and order parameters of the protein based on the assigned backbone chemical shifts. Our work lays the necessary foundation for further structural determination, dynamics characterization, and intermolecular interaction assay for the G131V mutant.

Structural Basis for the C-Terminal Domain of Mycobacterium tuberculosis Ribosome Maturation Factor RimM to Bind Ribosomal Protein S19.

Multidrug-resistant tuberculosis (TB) is a serious threat to public health, calling for the development of new anti-TB drugs. Chaperon protein RimM, involved in the assembly of ribosomal protein S19 into 30S ribosomal subunit during ribosome maturation, is a potential drug target for TB treatment. The C-terminal domain (CTD) of RimM is primarily responsible for binding S19. However, both the CTD structure of RimM from Mycobacterium tuberculosis (MtbRimMCTD) and the molecular mechanisms underlying MtbRimMCTD binding S19 remain elusive. Here, we report the solution structure, dynamics features of MtbRimMCTD, and its interaction with S19. MtbRimMCTD has a rigid hydrophobic core comprised of a relatively conservative six-strand ß-barrel, tailed with a short α-helix and interspersed with flexible loops. Using several biophysical techniques including surface plasmon resonance (SPR) affinity assays, nuclear magnetic resonance (NMR) assays, and molecular docking, we established a structural model of the MtbRimMCTD-S19 complex and indicated that the ß4-ß5 loop and two nonconserved key residues (D105 and H129) significantly contributed to the unique pattern of MtbRimMCTD binding S19, which might be implicated in a form of orthogonality for species-dependent RimM-S19 interaction. Our study provides the structural basis for MtbRimMCTD binding S19 and is beneficial to the further exploration of MtbRimM as a potential target for the development of new anti-TB drugs.

Role of metal cations and oxyanions in the regulation of protein arginine phosphatase activity of YwlE from Bacillus subtilis.

Protein arginine phosphorylation (pArg) is a relatively novel posttranslational modification. Protein arginine phosphatase YwlE negatively regulates arginine phosphorylation and consequently induces the expression of stress-response genes that are crucial for bacterial stress tolerance and pathogenic homolog Staphylococcus aureus virulence. However, little is known about the factors that affect the enzymatic activity of YwlE with the exception of the effect of oxidative stress. Herein, based on the hydrolysis of the chromogenic substrate p-nitrophenyl phosphate (pNPP) by YwlE, we investigate the role of metal cations and oxyanions in the regulation of YwlE activity. Interestingly, among the various cations that we tested, Ca2+ activates YwlE, while other cations, including Ag+, Co2+, Cd2+, and Zn2+, are inhibitory. Furthermore, as chemical analogues of phosphate, oxyanions play multiple roles in phosphatase activity. The regulatory switch Cys within the catalytic site regulates YwlE activity. Specifically, the thiol of this Cys could be alkylated by IAM (iodoacetamide) or oxidized by H2O2, resulting in enzymatic inhibition. Conversely, reducing reagents, such as DTT (dithiothreitol), ß-me (ß-mercaptoethanol), and TCEP (tris(2-carboxyethyl)phosphine) enhance YwlE activity. Additionally, as a stable analogue to pArg, pAIE binds to YwlE with a Kd of 149.1 nM and a binding stoichiometry n of 1.2 and inhibits YwlE with an IC50 of 316.3 ± 12.73 µM. The inhibition and activation of YwlE may have broad implications for the physiology, pharmacology and toxicology of metal cations and oxyanions.

Pulsed field gradient signal attenuation of restricted anomalous diffusions in plate, sphere, and cylinder with wall relaxation.

The effect of boundary relaxation on pulsed field gradient (PFG) anomalous restricted diffusion is investigated in this paper. The PFG signal attenuation expressions of anomalous diffusion in plate, sphere, and cylinder are derived based on fractional calculus. In addition, approximate expressions for boundary relaxation induced short time signal attenuation under zero gradient field and boundary relaxation affected short time apparent diffusion coefficients are given in this paper. Unlike the exponential signal attenuation in normal diffusion, the PFG signal attenuation in anomalous diffusion with boundary relaxation is either a Mittag-Leffler-function-based attenuation or a stretched-exponential-function-based attenuation. The stretched exponential attenuations of all three structures clearly show the diffractive pattern. In contrast, only in the plate structure does the Mittag-Leffler-function-based attenuation display an obvious diffractive pattern. Additionally, anomalous diffusion with smaller time derivative order α has a weaker diffractive pattern and less signal attenuation. Moreover, the results demonstrate that boundary relaxation induced signal attenuation is significantly affected by the anomalous diffusion when no gradient field is applied. Meanwhile, the boundary relaxation significantly affects PFG signal attenuation of anomalous diffusion in the following ways: The boundary relaxation results in reduced radius from the minimum of the diffractive patterns, and it results in an increased apparent diffusion coefficient and decreased surfaces to volume ratio in varying the diffusion time experiment; the boundary relaxation also substantially affects the apparent diffusion coefficient of sphere structure in the variation of gradient experiment.

Biophysical and functional characterizations of recombinant RimI acetyltransferase from Mycobacterium tuberculosis.

Nα-acetylation is a universal protein modification related to a wide range of physiological processes in eukaryotes and prokaryotes. RimI, an Nα-acetyltransferase in Mycobacterium tuberculosis, is responsible for the acetylation of the α-amino group of the N-terminal residue in the ribosomal protein S18. Despite growing evidence that protein acetylation may be correlated with the pathogenesis of tuberculosis, no structural information is yet available for mechanistically understanding the MtRimI acetylation. To enable structural studies for MtRimI, we constructed a serial of recombinant MtRimI proteins and assessed their biochemical properties. We then chose an optimal construct MtRimIC21A4-153 and expressed and purified the truncated high-quality protein for further biophysical and functional characterizations. The 2D 1H-15N heteronuclear single quantum coherence spectrum of MtRimIC21A4-153 exhibits wider chemical shift dispersion and favorable peak isolation, indicating that MtRimIC21A4-153 is amendable for further structural determination. Moreover, bio-layer interferometry experiments showed that MtRimIC21A4-153 possessed similar micromolar affinity to full-length MtRimI for binding the hexapeptide substrate Ala-Arg-Tyr-Phe-Arg-Arg. Enzyme kinetic assays also exhibited that MtRimIC21A4-153 had almost identical enzymatic activity to MtRimI, indicating insignificant influence of the recombinant variations on enzymatic functions. Furthermore, binding sites of the peptide were predicted by molecular docking approach, suggesting that this substrate binds to MtRimI primarily through electrostatic and hydrogen bonding interactions. Our results lay a foundation for the further structural determination and dynamics detection of MtRimI.

Solution structure and backbone dynamics for S1 domain of ribosomal protein S1 from Mycobacterium tuberculosis.

The pro-drug pyrazinamide is hydrolyzed to pyrazinoic acid (POA) in its use for the treatment of tuberculosis. As a molecule with bactericidal activity, POA binds to the C-terminal S1 domain of ribosomal protein S1 from Mycobacterium tuberculosis (MtRpsACTD_S1) to inhibit trans-translation. Trans-translation is a critical component of protein synthesis quality control, and is mediated by transfer-messenger RNA. Here, we have determined the solution structure of MtRpsACTD_S1(280-368), and analyzed its structural dynamics by NMR spectroscopy. The solution structure of MtRpsACTD_S1(280-368) mainly consists of five anti-parallel ß strands, two α helices, and two 310 helices. Backbone dynamics reveals that the overall structure of MtRpsACTD_S1(280-368) is rigid, but segment L326-V333 undergoes large amplitude fluctuations on picosecond to nanosecond time scales. In addition, residues V321, H322, V331 and D335 with large Rex values exhibit significant chemical or conformational exchange on microsecond to millisecond time scale. Titration of the truncated MtRpsACTD_S1(280-368) with POA shows similar characteristics to titration of MtRpsACTD_S1(280-438) with POA. In addition, diverse length fragments of MtRpsACTD_S1 show various HN resonance signals, and we find that the interaction of MtRpsA(369-481) with MtRpsACTD_S1(280-368) [Kd = (4.25 ± 0.15) mM] is responsible for the structural difference between MtRpsACTD_S1(280-368) and MtRpsACTD_S1. This work may shed light on the underlying molecular mechanism of MtRpsACTD recognizing and binding POA or mRNA, as well as the detailed mechanism of interactions between MtRpsACTD_S1(280-368) and the additional C-terminal MtRpsA(369-481).

Global exposure to rainstorms and the contribution rates of climate change and population change.

Quantifying global population exposure to rainstorms is a key component of population risk assessments for rainstorms and induced floods. Based on daily precipitation data from the NEX-GDDP dataset, rainfall from rainstorms is first calculated by a multi-model ensemble method for four periods from 1986 to 2100. Combined with population data from the SSP2 scenario, the global population exposure to rainstorms is then calculated and analyzed. Finally, the contribution rates of climate change effect, population change effect, and joint change effect on exposure change are quantitatively assessed. The results showed that (1) Population exposure to rainstorms shows a linear upward trend from base period to the late 21st century period in most regions, and the mid-21st century period compared with base period has the fastest rate of increase. (2) The spatial patterns of population exposure to rainstorms are very similar for the four periods and the areas with high exposure are mainly distributed in Asia, population exposure of Africa is gradually increasing. The countries with high exposure show little volatility, especially the top eight countries. (3) The change in total exposure is mainly due to population change. Based on the composition of the total exposure change for each country, the number of countries whose climate change effect is greater than that of population change is gradually increasing, and this number reaches more than a quarter of the total when the late 21st century period is compared with the mid-21st century period.

Structural basis for ribosome protein S1 interaction with RNA in trans-translation of Mycobacterium tuberculosis.

Ribosomal protein S1 (RpsA), the largest 30S protein in ribosome, plays a significant role in translation and trans-translation. In Mycobacterium tuberculosis, the C-terminus of RpsA is known as tuberculosis drug target of pyrazinoic acid, which inhibits the interaction between MtRpsA and tmRNA in trans-translation. However, the molecular mechanism underlying the interaction of MtRpsA with tmRNA remains unknown. We herein analyzed the interaction of the C-terminal domain of MtRpsA with three RNA fragments poly(A), sMLD and pre-sMLD. NMR titration analysis revealed that the RNA binding sites on MtRpsACTD are mainly located in the ß2, ß3 and ß5 strands and the adjacent L3 loop of the S1 domain. Fluorescence experiments determined the MtRpsACTD binding to RNAs are in the micromolar affinity range. Sequence analysis also revealed conserved residues in the mapped RNA binding region. Residues L304, V305, G308, F310, H322, I323, R357 and I358 were verified to be the key residues influencing the interaction between MtRpsACTD and pre-sMLD. Molecular docking further confirmed that the poly(A)-like sequence and sMLD of tmRNA are all involved in the protein-RNA interaction, through charged interaction and hydrogen bonds. The results will be beneficial for designing new anti-tuberculosis drugs.

Chemical shift assignments of Ribosomal protein S1 from Mycobacterium tuberculosis.

RpsA, also known as ribosomal protein S1, is an essential protein required for translation initiation of mRNAs when their Shine-Dalgarno sequence is degenerated (Sorensen et al. 1998). In addition, RpsA of Mycobacterium tuberculosis (M. tb) is involved in trans-translation, which is an effective system mediated by tmRNA-SmpB to release stalled ribosomes from mRNA in the presence of rare codons (Keiler 2008). Shi et al. found that POA binds to RpsA of Mtb and disrupts the formation of RpsA-tmRNA complex (Shi et al. 2011) and mutations at the C-terminus of RpsA confer PZA resistance. The previous work reported the pyrazinoic acid-binding domain of RpsA (Yang et al. Mol Microbiol 95:791-803, 2015). However, the HSQC spectra of the isolated S1 domain does not overlap with that of MtRpsA280-438, suggesting that substantial interactions occur between the flexible C-terminus and the S1 domain in MtRpsA .To further study the PZA resistance and how substantial interactions influence/affect protein structure, using heteronuclear NMR spectroscopy, we have completed backbone and side-chain 1H, 15N, 13C chemical shift assignments of MtRpsA280-438 which contains S1 domain and the flexible C-terminus. These NMR resonance assignments provide the framework for detailed characterization of the solution-state protein structure determination, dynamic studies of this domain, as well as NMR-based drug discovery efforts.

Signal attenuation of PFG restricted anomalous diffusions in plate, sphere, and cylinder.

Pulsed field gradient (PFG) NMR is a noninvasive tool to study anomalous diffusion, which exists widely in many systems such as in polymer or biological systems, in porous material, in single file structures and in fractal geometries. In a real system, the diffusion could be a restricted or a tortuous anomalous diffusion, rather than a free diffusion as the domains for fast and slow transport could coexist. Though there are signal attenuation expressions for free anomalous diffusion in literature, the signal attenuation formalisms for restricted anomalous diffusion is very limited, except for a restricted time-fractional diffusion within a plate reported recently. To better understand the PFG restricted fractional diffusion, in this paper, the PFG signal attenuation expressions were derived for three typical structures (plate, sphere, and cylinder) based on two models: fractal derivative model and fractional derivative model. These signal attenuation expressions include two parts, the time part Tn(t) and the space part Xn(r). Unlike normal diffusion, the time part Tn(t) in time-fractional diffusion can be either a Mittag-Leffler function from the fractional derivative model or a stretched exponential function from the fractal derivative model. However, provided the restricted normal diffusion and the restricted time-fractional diffusion are in an identical structure, they will have the same space part Xn(r) as both diffusions have the same space derivative parameter ß equaling 2, therefore, they should have similar diffractive patterns. The restricted general fractional diffusion within a plate is also investigated, which indicates that at a long time limit, the diffusion type is insignificant to the diffractive pattern that depends only on the structure and the gradient pulses. The expressions describing the time-dependent behaviors of apparent diffusion coefficient Df,app for restricted anomalous diffusion are also proposed in this paper. Both the short and long time-dependent behaviors of Df,app are distinct from that of normal diffusion. The general expressions for PFG restricted curvilinear diffusion of tube model were derived in a conventional way and its result agree with that obtained from the fractional derivative model with α equaling 1/2. Additionally, continuous-time random walk simulation was performed to give good support to the theoretical results. These theoretical results reported here will be valuable for researchers in analyzing PFG anomalous diffusion.

(1)H, (15)N, (13)C resonance assignments for pyrazinoic acid binding domain of ribosomal protein S1 from Mycobacterium tuberculosis.

Ribosomal protein S1 of Mycobacterium tuberculosis (MtRpsA) binds to ribosome and mRNA, and plays significant role in the regulation of translation initiation, conventional protein synthesis and transfer-messenger RNA (tmRNA) mediated trans-translation. It has been identified as the target of pyrazinoic acid (POA), a bactericidal moiety from hydrolysis of pyrazinamide, which is a mainstay of combination therapy for tuberculosis. POA prevented the interactions between the C-terminal S1 domain of MtRpsA (residues 280-368, MtRpsA(CTD)_S1) and tmRNA; so that POA can inhibit the trans-translation, which is a key component of multiple quality control pathways in bacteria. However, the details of molecular mechanism and dynamic characteristics for MtRpsA(CTD)_S1 interactions with POA, tmRNA or mRNA are still unclear. Here we present the (1)H, (15)N, (13)C resonance assignments of MtRpsA(CTD)_S1 as well as the secondary structure information based on backbone chemical shifts, which lay foundation for further solution structure determination, dynamic properties characterization and interactions investigation between MtRpsA(CTD)_S1 and tmRNA, RNA or POA.

ZIF-8 Cooperating in TiN/Ti/Si Nanorods as Efficient Anodes in Micro-Lithium-Ion-Batteries.

Zeolite imidazolate framework-8 (ZIF-8) nanoparticles embedded in TiN/Ti/Si nanorod (NR) arrays without pyrolysis have shown increased energy storage capacity as anodes for lithium ion batteries (LIBs). A high capacity of 1650 µAh cm(-2) has been achieved in this ZIF-8 composited multilayered electrode, which is ∼100 times higher than the plain electrodes made of only silicon NR. According to the electrochemical impedance spectroscopy (EIS) and (1)H nuclear magnetic resonance (NMR) characterizations, the improved diffusion of lithium ions in ZIF-8 and boosted electron/Li(+) transfer by the ZIF-8/TiN/Ti multilayer coating are proposed to be responsible for the enhanced energy storage ability. The first-principles calculations further indicate the favorable accessibility of lithium with appropriate size to diffuse in the open pores of ZIF-8. This work broadens the application of ZIF-8 to silicon-based LIBs electrodes without the pyrolysis and provides design guidelines for other metal-organic frameworks/Si composite electrodes.

Distinct effects of Cu2+-binding on oligomerization of human and rabbit prion proteins.

The cellular prion protein (PrP(C)) is a kind of cell-surface Cu(2+)-binding glycoprotein. The oligomerization of PrP(C) is highly related to transmissible spongiform encephalopathies (TSEs). Cu(2+) plays a vital role in the oligomerization of PrP(C), and participates in the pathogenic process of TSE diseases. It is expected that Cu(2+)-binding has different effects on the oligomerization of TSE-sensitive human PrP(C) (HuPrP(C)) and TSE-resistant rabbit PrP(C) (RaPrP(C)). However, the details of the distinct effects remain unclear. In the present study, we measured the interactions of Cu(2+) with HuPrP(C) (91-230) and RaPrP(C) (91-228) by isothermal titration calorimetry, and compared the effects of Cu(2+)-binding on the oligomerization of both PrPs. The measured dissociation constants (Kd) of Cu(2+) were 11.1 ± 2.1 µM for HuPrP(C) and 21.1 ± 3.1 µM for RaPrP(C). Cu(2+)-binding promoted the oligomerization of HuPrP(C) more significantly than that of RaPrP(C). The far-ultraviolet circular dichroism spectroscopy experiments showed that Cu(2+)-binding induced more significant secondary structure change and increased more ß-sheet content for HuPrP(C) compared with RaPrP(C). Moreover, the urea-induced unfolding transition experiments indicated that Cu(2+)-binding decreased the conformational stability of HuPrP(C) more distinctly than that of RaPrP(C). These results suggest that RaPrP(C) possesses a low susceptibility to Cu(2+), potentially weakening the risk of Cu(2+)-induced TSE diseases. Our work sheds light on the Cu(2+)-promoted oligomerization of PrP(C), and may be helpful for further understanding the TSE-resistance of rabbits.

Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide.

Pyrazinamide (PZA) is a first-line drug for tuberculosis (TB) treatment and is responsible for shortening the duration of TB therapy. The mode of action of PZA remains elusive. RpsA, the ribosomal protein S1 of Mycobacterium tuberculosis (Mtb), was recently identified as a target of PZA based on its binding activity to pyrazinoic acid (POA), the active form of PZA. POA binding to RpsA led to the inhibition of trans-translation. However, the nature of the RpsA-POA interaction remains unknown. Key questions include why POA exhibits an exquisite specificity to RpsA of Mtb and how RpsA mutations confer PZA resistance. Here, we report the crystal structures of the C-terminal domain of RpsA of Mtb and its complex with POA, as well as the corresponding domains of two RpsA variants that are associated with PZA resistance. Structural analysis reveals that POA binds to RpsA through hydrogen bonds and hydrophobic interactions, mediated mainly by residues (Lys303, Phe307, Phe310 and Arg357) that are essential for tmRNA binding. Conformational changes induced by mutation or sequence variation at the C-terminus of RpsA abolish the POA binding activity. Our findings provide insights into the mode of action of PZA and molecular basis of PZA resistance associated with RpsA mutations.

¹H, ¹³C, ¹5N backbone and side-chain resonance assignments of the human adenylate kinase 1 in apo form.

AK1 (Adenylate Kinase 1) plays crucial roles in processes such as cellular phosphotransfer networks, neuronal maturation and regeneration, gating of ABC transporter CFTR, tumor cell metabolism and myocardial energetic homeostasis. Here we report (1)H, (15)N and (13)C backbone and side-chain resonance assignments of the human AK1 protein in apo form. This work lays the essential basis for the further structure determination of hAK1.