Charge redistribution in proteins via linear hydrogen-bond chains (original) (raw)
Related papers
Proton Transfers in Enzyme and Ribozyme Active Sites
We will briefly discuss two biochemical problems where proton transfer (PT) plays a key role. In the first , we apply, using QM/MM simulations, a nontraditional picture for PT (in which the reaction coordinate is dominated by the rearrangement of the environment) to the initial rate-limiting enzymatic proton abstraction step in triosephosphate isomerase (TIM). Key groups involved in the environmental rearrangement of this enzymatic reaction and their energetic costs are identified. The contribution of multiple Valence Bond states to electronic structure along the reaction path is also discussed. In the second topic, we explore in an electronic structure study the role of PT in peptide bond formation (PBF), which involves a nucleophilic attack of an NH2 on an electrophilic carbonyl carbon. This is a crucial chemical step in the elongation cycle of protein synthesis, in the peptidyl transferase center (PTC) of the large ribosomal subunit, and the risome is known to be a ribozyme. The ...
Journal of the American Chemical Society, 1999
The values of electrophoretic mobility, µ electro , of bovine carbonic anhydrase II, human carbonic anhydrase II, cytochrome c, lysozyme, superoxide dismutase, ovalbumin, and derivatives of these proteins produced by partial neutralization of Lys -NH 3 + and/or Asp and Glu carboxyl groups were measured using capillary electrophoresis (CE). For derivatives of these proteins with the lowest overall values of net charge (either positive or negative), the values of µ electro and the values of charge measured by CE, Z CE , demonstrate a linear correlation with the number of charged groups, n, converted to neutral derivatives. For derivatives of these proteins with larger values of net charge, the values of µ electro and Z CE demonstrate a nonlinear correlation with n. Several observations made in this work suggest that shifts in the values of pk a of the ionizable groups on these proteins likely contribute to the observed nonlinear correlation. Debye-Hückel theory was used to calculate values of electrostatic potential at the surface of the derivatives of all six proteins from the measured values of µ electro . These values were plotted against the values of electrostatic potential calculated by assigning a charge to each protein in direct proportion to n. The data for all six proteins fell along a single common curve, regardless of the concentration of monovalent cations in the electrophoresis buffer.
Close pairs of carboxylates: a possibility of multicenter hydrogen bonds in proteins
Protein Engineering Design and Selection, 2003
Covalent attachment of hydrogen to the donor atom may be not an essential characteristic of stable hydrogen bonds. A positively charged particle (such as a proton), located between the two negatively charged residues, may lead to a stable interaction of the two negative residues. This paper analyzes close Asp-Glu pairs of residues in a large set of protein chains; 840 such pairs of residues were identified, of which 28% were stabilized by a metal ion, 12% by a positive residue nearby and 60% are likely to be stabilized by a proton. The absence of apparent structural constraints, secondary structure preferences, somewhat lower B-factors and a distinct correlation between pH and the minimal O-O distance in carboxylate pairs suggest that most of the abnormally close pairs could indeed be stabilized by a shared proton. Implications for protein stability and modeling are discussed.
The peptide group connecting Tyr440 and Ser441 of the bovine cytochrome c oxidase is involved in a recently proposed proton-transfer path (H-path) where, at variance with other pathways (D- and K-paths), a usual hydrogen-bond network is interrupted, thus making this proton propagation rather unconventional. Our density-functional based molecular dynamics simulations show that, despite this anomaly and provided that a proton can reach a nearby water, a multistep proton-transfer pathway can become a viable pathway for such a reaction: A proton is initially transferred to the carbonyl oxygen of a keto form of the Tyr440-Ser441 peptide group [−CO−NH−], producing an imidic acid [−C(OH)−NH−] as a metastable state; the amide proton of the imidic acid is then transferred, spontaneously to the deprotonated carboxyl group of the Asp51 side chain, leading to the formation of an enol form [−C(OH)N−] of the Tyr440-Ser441 peptide group. Then a subsequent enol-to-keto tautomerization occurs via a double proton-transfer path realized in the two adjacent Tyr440-Ser441 and Ser441-Asp442 peptide groups. An analysis of this multistep proton-transfer pathway shows that each elementary process occurs through the shortest distance, no permanent conformational changes are induced, thus preserving the X-ray crystal structure, and the reaction path is characterized by a reasonable activation barrier.
Proton-Coupled Electron Transfer in a Biomimetic Peptide as a Model of Enzyme Regulatory Mechanisms
Journal of the American Chemical Society, 2007
Proton-coupled electron-transfer reactions are central to enzymatic mechanism in many proteins. In several enzymes, essential electron-transfer reactions involve oxidation and reduction of tyrosine side chains. For these redox-active tyrosines, proton transfer couples with electron transfer, because the phenolic pKA of the tyrosine is altered by changes in the tyrosine redox state. To develop an experimentally tractable peptide system in which the effect of proton and electron coupling can be investigated, we have designed a novel amino acid sequence that contains one tyrosine residue. The tyrosine can be oxidized by ultraviolet photolysis or electrochemical methods and has a potential cross-strand interaction with a histidine residue. NMR spectroscopy shows that the peptide forms a-hairpin with several interstrand dipolar contacts between the histidine and tyrosine side chains. The effect of the cross-strand interaction was probed by electron paramagnetic resonance and electrochemistry. The data are consistent with an increase in histidine pK A when the tyrosine is oxidized; the effect of this thermodynamic coupling is to increase tyrosyl radical yield at low pH. The coupling mechanism is attributed to an interstrand π-cation interaction, which stabilizes the tyrosyl radical. A similar interaction between histidine and tyrosine in enzymes provides a regulatory mechanism for enzymatic electron-transfer reactions. Redox-active tyrosine residues mediate long-distance electrontransfer reactions in several enzymes. 1 For example, in photosystem II (PSII), Tyr 161 of the D1 polypeptide (Y Z) participates in water oxidation by reducing the primary donor P 680 + and by oxidizing the manganese cluster. 2 Tyr 160 in the D2 polypeptide (Y D) is also redox-active but is not required for water oxidation {reviewed in ref 3}. In addition to Y Z in PSII, tyrosyl radicals are essential for catalytic activity of prostaglandin H synthase, 4 ribonucleotide reductase (RNR), 5 and galactose oxidase. 6 Elucidation of the environmental factors, which influence the structure and function of the radical, will provide insights into the control of the activity in these enzymes. EPR studies of isotopically labeled tyrosinate have revealed that tyrosine oxidation occurs from the aromatic ring, generating a neutral radical with spin density located on the 1′, 3′, and 5′ carbon atoms and on the phenolic oxygen. 7,8 Additionally, rotation around the C 1′-C bond alters the EPR line shape. 7,8 In dipeptides, pentapeptides, and PSII, evidence for spin density delocalization to the amide group has been obtained {see ref 9 and references therein}. Oxidation of a protonated tyrosine at neutral pH values is coupled with the deprotonation of the phenolic oxygen. 10 This coupling of electron and proton transfer is due to a dramatic decrease in the pK A of the phenolic oxygen in the radical state. 10 Therefore, changes in the pK A of the proton-accepting group can alter the free energy of the oxidation/ reduction reaction. 11 In direct coupling reactions, the proton and electron movement may be simultaneous, sequential, or nonsynchronous. 12
Journal of the American Chemical Society, 2010
This paper combines two techniquessmass spectrometry and protein charge ladderssto examine the relationship between the surface charge and hydrophobicity of a representative globular protein (bovine carbonic anhydrase II; BCA II) and its rate of amide hydrogen-deuterium (H/D) exchange. Mass spectrometric analysis indicated that the sequential acetylation of surface lysine-ε-NH 3 + groupssa type of modification that increases the net negative charge and hydrophobicity of the surface of BCA II without affecting its secondary or tertiary structuresresulted in a linear decrease in the aggregate rate of amide H/D exchange at pD 7.4, 15°C. According to analysis with MS, the acetylation of each additional lysine generated between 1.4 and 0.9 additional hydrogens that are protected from H/D exchange during the 2 h exchange experiment at 15°C, pD 7.4. NMR spectroscopy demonstrated that none of the hydrogen atoms which became protected upon acetylation were located on the side chain of the acetylated lysine residues (i.e., lys-ε-NHCOCH 3 ) but were instead located on amide NHCO moieties in the backbone. The decrease in rate of exchange associated with acetylation paralleled a decrease in thermostability: the most slowly exchanging rungs of the charge ladder were the least thermostable (as measured by differential scanning calorimetry). This observationsthat faster rates of exchange are associated with slower rates of denaturationsis contrary to the usual assumptions in protein chemistry. The fact that the rates of H/D exchange were similar for perbutyrated BCA II (e.g., [lys-ε-NHCO(CH 2 ) 2 CH 3 ] 18 ) and peracetylated BCA II (e.g., [lys-ε-NHCOCH 3 ] 18 ) suggests that the electrostatic charge is more important than the hydrophobicity of surface groups in determining the rate of H/D exchange. These electrostatic effects on the kinetics of H/D exchange could complicate (or aid) the interpretation of experiments in which H/D exchange methods are used to probe the structural effects of non-isoelectric perturbations to proteins (i.e., phosphorylation, acetylation, or the binding of the protein to an oligonucleotide or to another charged ligand or protein).
Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2000
The coupled motion of electrons and protons occurs in many proteins. Using appropriate tools for calculation, the threedimensional protein structure can show how each protein modulates the observed electron and proton transfer reactions. Some of the assumptions and limitations involved in calculations that rely on continuum electrostatics to calculate the energy of charges in proteins are outlined. Approaches that mix molecular mechanics and continuum electrostatics are described. Three examples of the analysis of reactions in photosynthetic reaction centers are given: comparison of the electrochemistry of hemes in different sites; analysis of the role of the protein in stabilizing the early charge separated state in photosynthesis; and calculation of the proton uptake and protein motion coupled to the electron transfer from the primary (Q A ) to secondary (Q B ) quinone. Different mechanisms for stabilizing intra-protein charged cofactors are highlighted in each reaction. ß 2000 Elsevier Science B.V. All rights reserved.
Application of classical molecular dynamics for evaluation of proton transfer mechanism on a protein
Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2005
Proton transfer reactions on surfaces are prevalent in biology, chemistry and physics. In the present study, we employed classical Molecular Dynamics simulations to search for the presence of transient configurations that enable proton transfer, or proton sharing, between adjacent carboxylate groups on the protein surface. The results demonstrate that, during random fluctuations of the residues on the surface, there are repeated situations in which nearby carboxylates either share a common proton through a hydrogen bond, or are connected by a few water molecules that form conducting networks. These networks do not extend out of the common Coulomb cage of the participating residues and the lifetimes of the bridged structures are sufficiently long to allow passage of a proton between the carboxylates. The detection of domains capable of supporting a rapid proton transfer on a protein supports the notion that clusters of carboxylates are the operative elements of proton collecting antennae, as in bacteriorhodopsin, cytochrome c oxidase or the photosynthetic reaction center. D