Mössbauer, NMR, Geometric, and Electronic Properties in <i>S</i> = ³/₂ Iron Porphyrins

Mössbauer, NMR, Geometric, and Electronic Properties in S = 3/2 Iron Porphyrin

Deciphering the NMR Fingerprints of the Disordered System with Quantum Chemical Studies

Recent developments in solid-state NMR techniques helped acquire high-resolution NMR spectra for solid systems with structural disorder. But the structural origin of the observed chemical shift nonequivalence in these systems has not been revealed. We report a quantum chemical investigation of the solid-state NMR spectrum in N,N-bis(diphenylphosphino)-N-((S)-α-methylbenzyl)amine, where eight nonequivalent 31P NMR chemical shifts were resolved with a range of 13.0 ppm. Results from using different quantum chemical methods, computational algorithms, intermolecular effects, and structures indicate that for the disordered system, geometry optimization gives the best accord with experimental NMR chemical shifts, which has a theory-versus-experiment correlation R2 = 0.949 and SD = 1.1 ppm, or R2 = 0.994 and SD = 0.4 ppm when the average of two unassigned NMR shifts for each molecule is used. In addition, these calculations indicate that the experimental chemical shift nonequivalence in this system is mainly a consequence of the different geometries around the phosphorus atoms due to disordered environments. The experimental 31P NMR chemical shifts are well correlated (R2 = 0.981) with two conformation angles and one bond length, each associated with one of the three bonding interactions around the phosphorus atoms. These results will facilitate the use of quantum chemical techniques in structural characterization of disordered solids and elucidation of NMR properties

HNO Binding in a Heme Protein: Structures, Spectroscopic Properties, and Stabilities

HNO can interact with numerous heme proteins, but atomic level structures are largely unknown. In this work, various structural models for the first stable HNO heme protein complex, MbHNO (Mb, myoglobin), were examined by quantum chemical calculations. This investigation led to the discovery of two novel structural models that can excellently reproduce numerous experimental spectroscopic properties. They are also the first atomic level structures that can account for the experimentally observed high stabilities. These two models involve two distal His conformations as reported previously for MbCNR and MbNO. However, a unique dual hydrogen bonding feature of the HNO binding was not reported before in heme protein complexes with other small molecules such as CO, NO, and O₂. These results shall facilitate investigations of HNO bindings in other heme proteins

Structural, EPR Superhyperfine, and NMR Hyperfine Properties of the Cu−Octarepeat Binding Site in the Prion Protein

Previous experimental and computational investigations show that the copper binding in the prion protein that is involved in a number of neurodegenerative diseases is complicated and the exact binding structures remain to be determined. To facilitate structural investigation in this field, we report a quantum chemical investigation of structural, EPR superhyperfine, and NMR hyperfine properties of various copper complexes of the octarepeat domain, which has several copies of highly conserved amino acid sequence of PHGGGWGQ. The predicted metal−ligand bond lengths of the X-ray structure of CuHGGGW, involving the central five residues in this domain, from the best method examined here, have a mean absolute deviation (MAD) of 0.030 Å, basically the same as found with experimental errors of various metal complexes. Prior controversial results regarding water coordination were resolved here with a more extensive computational investigation on 10 models with various water molecules and sequences (both HGGGW and PHGGGWGQ), which are consistent with the experimental reports. Experimental EPR superhyperfine constants are accurately reproduced with a MAD of 0.95 MHz. Results here suggest that the NMR hyperfine shifts which can be readily measured in NMR experiments and accurately predicted in quantum chemical calculations can provide more extensive and more sensitive structural probes than those from the current EPR studies. These results will be helpful for future experimental and computational investigations of the copper binding structures of the prion protein as well as other related systems

The region of TFIIS containing the LW motif mediates a protein–protein interaction

<p><b>Copyright information:</b></p><p>Taken from "A sequence motif conserved in diverse nuclear proteins identifies a protein interaction domain utilised for nuclear targeting by human TFIIS"</p><p>Nucleic Acids Research 2006;34(8):2219-2229.</p><p>Published online 28 Apr 2006</p><p>PMCID:PMC1450333.</p><p>© The Author 2006. Published by Oxford University Press. All rights reserved</p> Pull-down assay of S-labelled hIWS1 binding to immobilized GST-fusion proteins containing regions of TFIIS (indicated above the lanes). Graphical representation of this data is shown below in comparison with 20% of the labelled input protein and a pull-down using GST alone

Unprecedented Fe(IV) Species in a Diheme Protein MauG: A Quantum Chemical Investigation on the Unusual Mössbauer Spectroscopic Properties

Ferryl species are important catalytic intermediates in heme enzymes. A recent experimental investigation of a diheme protein MauG reported the first case of using two Fe(IV) species as an alternative to compound I in catalysis. Both Fe(IV) species have unusual Mössbauer properties, which was found to originate from novel structural features based on a quantum chemical investigation. With comparison with the previously reported Fe^IVO and Fe^IV−OH species, results here provide evidence of new mechanisms by which proteins influence the properties of ferryl species by directly providing the O via Tyr or stabilizing exogenous O via hydrogen bonding interaction. These results expand our ability to identify and evaluate high-valent heme proteins and models

NMR, IR/Raman, and Structural Properties in HNO and RNO (R = Alkyl and Aryl) Metalloporphyrins with Implication for the HNO−Myoglobin Complex

Structural and functional details of heme protein complexes with HNO and the isoelectronic RNO (R = alkyl and aryl) molecules (metabolic intermediates) are largely unknown. We report a quantum chemical investigation of three characteristic spectroscopic properties, 1H and 15N NMR chemical shifts and NO vibrational frequencies in synthetic HNO and RNO heme complexes, with theory-versus-experiment correlation coefficients R2 = 0.990−0.998. A new density functional theory (DFT) method was found to yield excellent predictions of experimental structures of HNO, RNO, and NO heme systems. Interestingly, this method also helps the identification of an excellent linear quantitative structure observable relationship between NO vibrational frequencies and bond lengths in all of these NO-containing systems. This suggests that NO vibrations are largely local effects of the NO bonds in these complexes and may help deduce the NO bond lengths from using experimental vibrational data in these systems. The NO vibrational frequencies in HNO, RNO, and NO metalloporphyrins were found to follow a general trend of NO > RNO > HNO complexes, as a result of the electron populations in the antibonding NO orbitals of NO 1H and 15N NMR results and NO vibrational frequency in MbHNO, a dual hydrogen-bond mode for HNO in MbHNO was proposed. The enhanced stability from this dual hydrogen bonding may provide a basis for the unusual stability of MbHNO observed experimentally. These results should facilitate spectroscopic characterizations and structural investigations of HNO and RNO heme proteins and models

Table1_Prevalence and adverse outcomes of pre-operative frailty in patients undergoing carotid artery revascularization: a meta-analysis.docx

IntroductionFrailty can lead to a decrease in the patient's resistance to interference such as injury and disease, and cause a series of complications. An increasing number of studies have found that pre-operative frailty exacerbates the occurrence of adverse events after carotid artery revascularization, but an integrated quantitative analysis is currently lacking. Therefore, we conducted a meta-analysis to evaluate the impact of pre-operative frailty on patients undergoing carotid artery revascularization.MethodAccording to the PRISMA guidelines, we systematically searched for relevant studies on Medline, Embase, Ovid, CINAHL, Web Of Science, and Cochrane Library from establishment until June 2023. Summarize the risk of adverse outcome events through OR and 95% CI.ResultsA total of 16 cohort studies were included, including 1692338 patients. Among patients who underwent carotid artery revascularization surgery, the prevalence of pre-operative frailty was 36% (95% CI = 0.18–0.53, P 2 = 94%), stroke (OR = 1.33, 95% CI = 1.10–1.61, P = 0.003, I2 = 71%), myocardial infarction (OR = 1.86, 95% CI = 1.51–2.30, P 2 = 61%), and non-home discharge (OR = 2.39, 95% CI = 1.85–3.09, P 2 = 63%).ConclusionThe results of this article show that patients undergoing carotid artery revascularization have a higher prevalence of pre-operative frailty, which can lead to an increased risk of postoperative death, stroke, myocardial infarction, and non-home discharge. Strengthening the assessment and management of frailty is of great significance for patient prognosis.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=416234, identifier: CRD42023416234.</p

Table_1_Long Non-coding Antisense RNA TNRC6C-AS1 Is Activated in Papillary Thyroid Cancer and Promotes Cancer Progression by Suppressing TNRC6C Expression.DOCX

<p>Context: Evidences have shown the important role of long non-coding antisense RNAs in regulating its cognate sense gene in cancer biology.</p><p>Objective: Investigate the regulatory role of a long non-coding antisense RNA TNRC6C-AS1 on its sense partner TNRC6C, and their effects on the aggressiveness and iodine-uptake ability of papillary thyroid cancer (PTC).</p><p>Design: TNRC6C-AS1 was identified as the target long non-coding RNA in PTC by using microarray analysis and computational analysis. In vitro gain/loss-of-function experiments were performed to investigate the effects of TNRC6C-AS1 and TNRC6C on proliferation, apoptosis, migration, invasion and iodine-uptake ability of TPC1 cells. Expression levels of TNRC6C-AS1 and TNRC6C of 30 cases of PTC tissues and its adjacent normal thyroid tissues were determined.</p><p>Results: Downregulation of TNRC6C-AS1 or overexpression of TNRC6C inhibited proliferation, migration and invasion of TPC1 cells, while apoptosis and iodine uptake was promoted in TPC1 cells. Suppression of TNRC6C-AS1 significantly increased the expression of TNRC6C in TPC1 cells. The inhibitory effect of TNRC6C-AS1 knockdown on cell proliferation, migration and invasion was attenuated when the expression of TNRC6C was suppressed simultaneously, indicating TNRC6C is a functional target of TNRC6C-AS1. The expression of TNRC6C-AS1 was significantly higher, while the TNRC6C mRNA and protein were significantly lower in PTC tissues than normal adjacent tissues. There was a significant inverse correlation between TNRC6C-AS1 and TNRC6C mRNA in PTC tissue samples.</p><p>Conclusions: TNRC6C-AS1 promotes the progression of PTC and inhibits its ability of iodine accumulation by suppressing the expression of TNRC6C. Targeting TNRC6C-AS1 - TNRC6C axis may be a new promising treatment for PTC.</p

Evaluating the Intrinsic Cysteine Redox-Dependent States of the A-Chain of Human Insulin Using NMR Spectroscopy, Quantum Chemical Calculations, and Mass Spectrometry

Previous functional studies have proposed that solution-phase loading of human insulin A-chain peptides into cell surface Class II molecules may be limited by the redox state of intrinsic cysteine residues within the A-chain peptide. T cell functional studies of a human insulin A-chain analogue (KR A1−15) comprised of residues 1−15 of the A-chain peptide as well as an amino-terminal lysine-arginine extension have been carried out in a reducing environment. These data suggest that free thiol moieties within this peptide may participate in major histocompatibility complex (MHC) II/peptide interactions. Two-dimensional 1H NMR spectroscopy data partnered with quantum chemical calculations identified that KR A1−15 exists in conformational flux sampling heterogeneous redox-dependent conformations including: one reduced and two oxidized states. These findings were further supported by mass spectrometry analysis of this peptide that confirmed the presence of a redox state dependent conformational equilibrium. Interestingly, the presence of a free thiol (1Hγ) resonance for cysteine 8 in the oxidized state supports the existence of the third redox-dependent conformation represented as a mixed disulfide conformation. We believe these data support the presence of a redox-dependent mechanism for regulating the activity of human insulin and provide a better understanding of redox chemistry that may be extended to other protein systems