Identification of histidine-122alpha in human haemoglobin as one of the unknown alkaline Bohr groups by hydrogen--tritium exchange.
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ABSTRACT:
SUBMITTER: Nishikura K
PROVIDER: S-EPMC1185820 | biostudies-other | 1978 Aug
REPOSITORIES: biostudies-other
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Project description:1. Four histidine-containing peptides have been isolated from a tryptic digest of the Zn2+-requiring beta-lactamase II from Bacillus cereus. One of these peptides probably contains two histidine residues. 2. The presence of one equivalent of Zn2+ substantially decreases the rate of exchange of the C-2 proton in at least two and probably three of the histidine residues of these peptides for solvent 3H. 3. It is concluded that peptides containing at least two of the three histidine residues acting as Zn2+ ligands at the tighter Zn2+-binding site of beta-lactamase II have been identified.
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Project description:Histidine Hydrogen-Deuterium Exchange Mass Spectrometry (His-HDX-MS) determines the HDX rates at the imidazole C(2)-hydrogen of histidine residues. This method provides not only the HDX rates but also the pK(a) values of histidine imidazole rings. His-HDX-MS was used to probe the microenvironment of histidine residues of E. coli dihydrofolate reductase (DHFR), an enzyme proposed to undergo multiple conformational changes during catalysis.Using His-HDX-MS, the pK(a) values and the half-lives (t(1/2)) of HDX reactions of five histidine residues of apo-DHFR, DHFR in complex with methotrexate (DHFR-MTX), DHFR in complex with MTX and NADPH (DHFR-MTX-NADPH), and DHFR in complex with folate and NADP+ (DHFR-folate-NADP+) were determined. The results showed that the two parameters (pK(a) and t(1/2)) are sensitive to the changes of the microenvironment around the histidine residues. Although four of the five histidine residues are located far from the active site, ligand binding affected their pK(a), t(1/2) or both. This is consistent with previous observations of ligand binding-induced distal conformational changes on DHFR. Most of the observed pK(a) and t(1/2) changes could be rationalized using the X-ray structures of apo-DHFR, DHFR-MTX-NADPH, and DHFR-folate-NADP+. The availability of the neutron diffraction structure of DHFR-MTX enabled us to compare the protonation states of histidine imidazole rings.Our results demonstrate the usefulness of His-HDX-MS in probing the microenvironments of histidine residues within proteins.
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Project description:Isotope exchange at the histidine C2 atom of imidazole in D2O solution is well known to occur at a significantly slower rate than the exchange of amide protons. Analysis of the kinetics of this isotope-exchange reaction is proposed herein as a method of detecting histidine phosphorylation. This modification of His-containing peptides is challenging to pinpoint because of its instability under acidic conditions as well as during CID-MS analysis. In this work, we investigated the effect of phosphorylation of the histidine side chain in peptides on deuterium-hydrogen exchange (DHX) in the imidazole. The results demonstrate that phosphorylation dramatically slows the rate of the DHX reaction. This phenomenon can be applied to detect phosphorylation of peptides at the histidine residue (e.g., in enzymatic digests). We also found that the influence of the peptide sequence on the exchange kinetics is relatively small. A CID fragmentation experiment revealed that there was no detectable hydrogen scrambling in peptides deuterated at C2 of the imidazole ring. Therefore, MS/MS can be used to directly identify the locations of deuterium ions incorporated into peptides containing multiple histidine moieties.
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Project description:In this work, we have developed a method that uses hydrogen-deuterium exchange (HDX) of C2-hydrogens of histidines coupled with mass spectrometry (MS) to identify Zn-bound histidines in metalloproteins. This method relies on differences in HDX reaction rates of Zn-bound and Zn-free His residues. Using several model peptides and proteins, we find that all Zn-bound His residues have substantially lower HDX reaction rates in the presence of the metal. The vast majority of non-Zn-binding His residues undergo no significant changes in HDX reaction rates when their reactivity is compared in the presence and absence of Zn. Using this new approach, we then determined the Zn binding site of ?-2-microglobulin, a protein associated with metal-induced amyloidosis. Together, these results suggest that HDX-MS of His C2-hydrogens is a promising new method for identifying Zn-bound histidines in metalloproteins.
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Project description:Both experimental and computational methods are available to gather information about a protein's conformational space and interpret changes in protein structure. However, experimentally observing and computationally modeling large proteins remain critical challenges for structural biology. Our work aims at addressing these challenges by combining computational and experimental techniques relying on each other to overcome their respective limitations. Indeed, despite its advantages, an experimental technique such as hydrogen-exchange monitoring cannot produce structural models because of its low resolution. Additionally, the computational methods that can generate such models suffer from the curse of dimensionality when applied to large proteins. Adopting a common solution to this issue, we have recently proposed a framework in which our computational method for protein conformational sampling is biased by experimental hydrogen-exchange data. In this paper, we present our latest application of this computational framework: generating an atomic-resolution structural model for an unknown protein state. For that, starting from an available protein structure, we explore the conformational space of this protein, using hydrogen-exchange data on this unknown state as a guide. We have successfully used our computational framework to generate models for three proteins of increasing size, the biggest one undergoing large-scale conformational changes.
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Project description:G protein-coupled receptors (GPCRs) are activated by ligand binding, allowing extracellular signals to be efficiently transmitted through the membrane to the G protein recognition site, 40 Å away. Utilizing His residues found spaced throughout the GPCR, rhodopsin, we used His hydrogen-deuterium exchange (His-HDX) to monitor long-time scale structural rearrangements previously inaccessible by other means. The half-lives of His-HDX indicate clear differences in the solvent accessibility of three His residues in rhodopsin/opsin and Zn2+-dependent changes in the pKa for His195. These results indicate the utility of His-HDX in examining structural rearrangements in native source and membrane proteins without requiring structural modification.
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Project description:NMR scalar couplings across hydrogen bonds represent direct evidence for the partial covalent nature of hydrogen bonds and provide structural and dynamic information on hydrogen bonding. In this article, we report heteronuclear 15N-31P and 1H-31P scalar couplings across the intermolecular hydrogen bonds between protein histidine (His) imidazole and DNA phosphate groups. These hydrogen-bond scalar couplings were observed for the Egr-1 zinc-finger-DNA complex. Although His side-chain NH protons are typically undetectable in heteronuclear 1H-15N correlation spectra due to rapid hydrogen exchange, this complex exhibited two His side-chain NH signals around 1H 14.3 ppm and 15N 178 ppm at 35 °C. Through various heteronuclear multidimensional NMR experiments, these signals were assigned to two zinc-coordinating His side chains in contact with DNA phosphate groups. The data show that the Nδ1 atoms of these His side chains are protonated and exhibit the 1H-15N cross-peaks. Using heteronuclear 1H, 15N, and 31P NMR experiments, we observed the hydrogen-bond scalar couplings between the His 15Nδ1/1Hδ1 and DNA phosphate 31P nuclei. These results demonstrate the direct involvement of the zinc-coordinating His side chains in the recognition of DNA by the Cys2His2-class zinc fingers in solution.
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Project description:The oxygen functionalization of carbon materials has widely been employed to improve the catalytic performance of carbon-supported Pt (Pt/C) catalysts. Hydrochloric acid (HCl) has often been employed to clean carbons during the preparation of carbon materials. However, the effect of oxygen functionalization through a HCl treatment of porous carbon (PC) supports on the performance of the alkaline hydrogen evolution reaction (HER) has rarely been investigated. Herein, the impact of HCl combined with the heat treatment of PC supports on the HER performance of Pt/C catalysts has been comprehensively investigated. The structural characterizations revealed similar structures of pristine and modified PC. Nevertheless, the HCl treatment resulted in abundant hydroxyl and carboxyl groups and the further heat treatment formed thermally stable carbonyl and ether groups. Among the catalysts, Pt loading on the HCl-treated PC followed by a heat treatment at 700 °C (Pt/PC-H-700) exhibited elevated HER activity with a lower overpotential of 50 mV at 10 mA cm-2 when compared to the unmodified Pt/PC (89 mV). Pt/PC-H-700 also exhibited better durability than the Pt/PC. Overall, novel insights into the impact of the surface chemistry properties of porous carbon supports on the HER performance of Pt/C catalysts were provided, which were useful for highlighting the feasible improvement of HER performances by regulating the surface oxygen species of porous carbon supports.
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Project description:The physicochemical and mechanical properties of new alkaline anion-exchange membranes (AAEMs) based on chitosan (CS) and poly(vinyl alcohol) (PVA) polymers doped with unsupported copper nanoparticles (NPs) and copper exchanged over different porous materials were investigated regarding ion-exchange capacity (IEC), OH- conductivity, water uptake (WU), water vapor permeability (WVP), and thermal and mechanical resistance. The influence of the type of filler included in different morphologies and filler loading has been explored using copper exchanged materials such as the layered porous titanosilicate AM-4, layered stannosilicate UZAR-S3, and zeolites Y, MOR, and BEA. Compared to commercially available anion-exchange membranes, the best performing membranes in terms of WU, IEC, OH- conductivity and WVP in this study were those containing 10 wt % of Cu-AM-4 and Cu-UZAR-S3, although 10 wt % Cu-MOR provided better mechanical strength at close values of WVP and anion conductivity. It was also observed that when Cu was exchanged in a porous silicate matrix, its oxidation state was lower than when embedded as unsupported metal NPs. In addition, the statistical analysis of variance determined that the electrochemical properties of the membranes were noticeably affected by both the type and filler loading, and influenced also by the copper oxidation state and content in the membrane, but their hydrophilic properties were more affected by the polymers. The largest significant effects were noticed on the water sorption and transport properties, which gives scope for the design of AAEMs for electrochemical and water treatment applications.
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