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Histidine Side Chain (histidine + side_chain)
Selected AbstractsStereoselectivity of Pseudomonas cepacia lipase toward secondary alcohols: A quantitative modelPROTEIN SCIENCE, Issue 6 2000Tanja Schulz Abstract The lipase from Pseudomonas cepacia represents a widely applied catalyst for highly enantioselective resolution of chiral secondary alcohols. While its stereopreference is determined predominantly by the substrate structure, stereoselectivity depends on atomic details of interactions between substrate and lipase. Thirty secondary alcohols with published E values using P. cepacia lipase in hydrolysis or esterification reactions were selected, and models of their octanoic acid esters were docked to the open conformation of P. cepacia lipase. The two enantiomers of 27 substrates bound preferentially in either of two binding modes: the fast-reacting enantiomer in a productive mode and the slow-reacting enantiomer in a nonproductive mode. Nonproductive mode of fast-reacting enantiomers was prohibited by repulsive interactions. For the slow-reacting enantiomers in the productive binding mode, the substrate pushes the active site histidine away from its proper orientation, and the distance d(HN, , Oalc) between the histidine side chain and the alcohol oxygen increases. d(HN, , Oalc) was correlated to experimentally observed enantioselectivity: in substrates for which P. cepacia lipase has high enantioselectivity (E > 100), d(HN, , Oalc) is>2.2 Å for slow-reacting enantiomers, thus preventing efficient catalysis of this enantiomer. In substrates of low enantioselectivity (E < 20), the distance d(HN, , Oalc) is less than 2.0 Å, and slow- and fast-reacting enantiomers are catalyzed at similar rates. For substrates of medium enantioselectivity (20 < E< 100), d(HN, , Oalc) is around 2.1 Å. This simple model can be applied to predict enantioselectivity of P. cepacia lipase toward a broad range of secondary alcohols. [source] Comparison of collision- versus electron-induced dissociation of Pt(II) ternary complexes of histidine- and methionine-containing peptides,RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2009Linda Feketeová Incubation of the histidine-containing peptides (GH, HG, GGH, GHG, HGG) and methionine-containing peptides (GM, MG, GGM, GMG, MGG) with the platinum complexes [Pt(terpy)Cl]+ (A) and [Pt(dien)Cl]+ (B) followed by electrospray ionisation (ESI) led to a number of singly and doubly charged ternary platinum peptide complexes, including [Pt(L)M]2+ and [Pt(L)M,H]+ (where L,=,the ligand terpy or dien; M is a peptide). Each of the [Pt(L)M]2+ complexes was subjected to electron capture dissociation (ECD), collision-induced dissociation (CID) and electron-induced dissociation (EID), while each of the [Pt(L)M,H]+ complexes was subjected to CID and EID. Results from ECD suggest that the free electron is captured by the metal ion thus weakening the bonds to its ligands. In the case of the ligand terpy, which binds more strongly than dien, this weakening leads to the loss of the peptide. The minor products in the ECD spectra of [Pt(terpy)M]2+ complexes do show fragmentation along the peptide backbone, but the ions observed are of the a-, b-, and y-type. For the complexes with methionine-containing peptides, a marker ion, [Pt(L)SCH3]+, was found which is indicative of binding of Pt to the methionine side chain. For the histidine-containing peptides, an ion containing platinum, the auxiliary ligand, and the histidine imine was observed in many instances, thus indicating the binding of the histidine side chain to the metal, but other modes of Pt coordination (N-terminus) were also found to be competitive. These findings are consistent with a recent finding (Sze et al. J. Biol. Inorg. Chem. 2009; 14: 163) that Pt occupies the methionine-rich copper(I)-binding site rather than histidine-rich copper(II)-binding site in the CopC protein. Copyright © 2009 John Wiley & Sons, Ltd. [source] Active-site changes in the pyruvate dehydrogenase multienzyme complex E1 apoenzyme component from Escherichia coli observed at 2.32,Å resolutionACTA CRYSTALLOGRAPHICA SECTION D, Issue 11 2006Palaniappa Arjunan The first enzymatic component, E1 (EC 1.2.4.1), of the pyruvate dehydrogenase multienzyme complex (PDHc) utilizes thiamine diphosphate (ThDP) and Mg2+ as cofactors. The structure of a branched-chain-specific E1 apoenzyme from the heterotetrameric ,2,2 E1 family was recently reported and showed that disorder-to-order transformations in two active-site loops take place upon cofactor binding. To ascertain what effect the absence of cofactor may have in the homodimeric ,2Escherichia coli PDHc E1, the corresponding apoenzyme has been prepared and its three-dimensional structure determined and analyzed at 2.32,Å by crystallographic methods. This represents the first reported apoenzyme structure for any E1 component from the homodimeric ,2 family. Electron-density features occurring in the region where the cofactor pyrimidine ring would normally be expected to bind are of size, shape and location compatible with water molecules that form a hydrogen-bonded linkage between residues Glu571 and Val192, which normally make conserved interactions with the ThDP cofactor. A histidine side chain that normally forms hydrogen bonds to ThDP is disordered in its absence and partially occupies two sites. Unlike in the reported heterotetrameric branched-chain apo-E1, no disorder/order loop transformations are evident in apo-PDHc E1 relative to the holo-E1 enzyme (PDHc E1,ThDP,Mg2+). Differences in the extent of hydrogen-bonding networks found in the apo-E1 enzyme, the holo-E1 enzyme and in an inhibitor complex with bound thiamine 2-thiazolone diphosphate (ThTDP), PDHc E1,ThTDP,Mg2+, are described. [source] Synthesis and Esterolytic Activity of Catalytic Peptide DendrimersCHEMISTRY - A EUROPEAN JOURNAL, Issue 5 2004David Lagnoux Abstract Peptide dendrimers were prepared by solid-phase peptide synthesis. Monomeric dendrimers were first obtained by assembly of a hexapeptide sequence containing alternate standard , -amino acids with diamino acids as branching units. The monomeric dendrimers were then dimerized by disulfide-bridge formation at the core cysteine. The synthetic strategy is compatible with functional amino acids and different diamino acid branching units. Peptide dendrimers composed of the catalytic triad amino acids histidine, aspartate, and serine catalyzed the hydrolysis of N -methylquinolinium salts when the histidine residues were placed at the outermost position. The dendrimer-catalyzed hydrolysis of 7-isobutyryl- N -methylquinolinium followed saturation kinetics with a rate constant of catalysis/rate constant without catalysis (kcat/kuncat) value of 3350 and a rate constant of catalysis/Michaelis constant (kcat/KM) value 350-fold larger than the second-order rate constant of the 4-methylimidazole-catalyzed reaction; this corresponds to a 40-fold rate enhancement per histidine side chain. Catalysis can be attributed to the presence of histidine residues at the surface of the dendrimers. [source] Characterisation of FXTAS related isolated intranuclear protein inclusions using laser tweezers Raman spectroscopyJOURNAL OF RAMAN SPECTROSCOPY, Issue 1 2010Tobias J. Moritz Abstract We report the analysis of the vibrational modes of intranuclear protein inclusions isolated from the brain of human subjects with the Fragile X-associated tremor/ataxia syndrome (FXTAS). In this preliminary study, Raman spectra of optically trapped inclusions were measured and analysed to determine protein composition and structure. Our main findings are as follows: (1) The spectra of protein inclusions are characteristic of H2A and H2B histones, which correlate with previous mass spectrometry (MS) studies; (2) Tyrosine is present in its OH form and exposed at the protein surface; (3) Zn and to a lesser extent Cu bound to histidine side chains are detected in the inclusions; (4) The tryptophan side-chain torsion angle is calculated to be 102°; (5) Several potential spectroscopic markers for the inclusions of FXTAS are identified. These results show the capability of using laser tweezers Raman spectroscopy to identify protein inclusions in a non-perturbative way and to gain further insight into the pathogenesis and progression of FXTAS in human subjects and in experimental models of this disorder. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||