Histidine Molecules Research Articles

Design and synthesis of new biomimetic materials

In this paper, it is reported that the histidine-silane derivative Boc-His(Boc)-CONH-(CH 2) 3Si(OEt) 3 can be polymerized via the sol-gel method or can be grafted on a silica surface. The obtained organosilicas bear histidine molecules covalently bonded on the inorganic matrix. Their Cu(II) complexes have been evaluated as oxidation catalysts for the conversion of 3,5-di- tert-butylcatechol (DTBC) to 3,5-di- tert-butylquinone (DTBQ) in the presence of dioxygen.

Potentiometric and spectroscopic studies of reactions of histidine with 13-membered amide-based macrocyclic Cu 2+ chelates

The Cu 2+ complex of a 13-membered macrocycle, 2,9-dioxo-1,4,7,10-tetraaza-4,7-cyclotridecanediacetic acid (abbreviated as LH 2), formed histidine adducts in which a histidine molecule occupied a secondary coordination site of the macrocyclic Cu 2+ chelate. The formation of these adducts was observed as a change in the d–d band of the macrocyclic Cu 2+ chelate in the presence of histidine at different pH values. The compositions of the species were determined by potentiometric titration, and the formation constants were obtained as: log[CuL(hdH)]/[CuL][hdH]=2.8(0.2) and log[Cu(LH −2)(hdH)]/[Cu(LH −2)][hdH]=2.6(0.4) (hd=histidinate(−1) ion; LH −2=L with deprotonated amide nitrogen atoms). These adducts are formed by the coordination of the imidazole ring nitrogen atom to the central metal ion, and are stabilized by an interaction (such as hydrogen bond formation) between the pendant arms of the macrocyclic chelate and the substrate.

Histidase from the unicellular green alga Dunaliella tertiolecta: purification and partial characterization

In summer, the concentrations of dissolved organic nitrogen compounds are often higher than that of inorganic nitrogen. Under such conditions it would be advantageous if phytoplankton species could utilize organic nitrogen sources, including free or combined amino acids, in addition to inorganic nitrogen. This study focused on histidine, the degradation of which potentially yields three nitrogen atoms for each molecule of histidine. In this work, histidase from Dunaliella tertiolecta, a deaminating enzyme catalysing the first steps of histidine degradation, was purified 4000-fold and partially characterized. The molecular weight of the native enzyme was estimated to be 155 kDa, corresponding to four subunits of 38 kDa. D. tertiolecta histidase is stable in the presence of dithiothreitol and is inactivated by cyanide. Histidinol phosphate, histidine and Mn2+ are effective protectors against cyanide inactivation. The enzyme did not exhibit classical Michaelis-Menten kinetics but showed a relationship between the rate of catalysis (V) and the concentration of substrate (S) that was characteristic of negative allosteric behaviour. A Hill coefficient of 4 was measured for histidine concentrations higher than 22.5 mM. Guanine, xanthine and cytosine nucleotides are inhibitors of D. tertiolecta histidase.

Histidase from the unicellular green alga Dunaliella tertiolecta: purification and partial characterization

In summer, the concentrations of dissolved organic nitrogen compounds are often higher than that of inorganic nitrogen. Under such conditions it would be advantageous if phytoplankton species could utilize organic nitrogen sources, including free or combined amino acids, in addition to inorganic nitrogen. This study focused on histidine, the degradation of which potentially yields three nitrogen atoms for each molecule of histidine. In this work, histidase from Dunaliella tertiolecta, a deaminating enzyme catalysing the first steps of histidine degradation, was purified 4000-fold and partially characterized. The molecular weight of the native enzyme was estimated to be 155 kDa, corresponding to four subunits of 38 kDa. D. tertiolecta histidase is stable in the presence of dithiothreitol and is inactivated by cyanide. Histidinol phosphate, histidine and Mn2+ are effective protectors against cyanide inactivation. The enzyme did not exhibit classical Michaelis-Menten kinetics but showed a relationship between the rate of catalysis (V) and the concentration of substrate (S) that was characteristic of negative allosteric behaviour. A Hill coefficient of 4 was measured for histidine concentrations higher than 22.5 mM. Guanine, xanthine and cytosine nucleotides are inhibitors of D. tertiolecta histidase.

Thermal behaviour of RE(HIS)(NO3)3.H2O

The thermal decomposition behaviour of the complexes of rare earth metals with histidine: RE(His)(NO3)3⋅H2O (RE=La—Nd, Sm—Lu and Y; His=histidine) was investigated by means of TG-DTG techniques. The results indicated that the thermal decomposition processes of the complexes can be divided into three steps. The first step is the loss of crystal water molecules or part of the histidine molecules from the complexes. The second step is the formation of alkaline salts or mixtures of nitrates with alkaline salts after the histidine has been completely lost from the complexes. The third step is the formation of oxides or mixtures of oxides with alkaline salts. The results relating to the three steps indicate that the stabilities of the complexes increase from La to Lu.

Design and Synthesis of New Biomimetic Materials by Sol-Gel: A Cu(II)(histidine)(2) Complex Covalently Bonded on a Silica Matrix.

The synthesis of a new histidine-silane derivative, Boc-His(Boc)-CONH-(CH(2))(3)Si(OEt)(3), is reported. Hydrolysis and co-condensation of this monomer with tetraethoxysilane, via the sol-gel procedure, results in a hybrid inorganic-organic material that bears histidine molecules covalently bonded on a silica matrix. 1D-ESEEM and 2D-HYSCORE studies of its Cu(II) complex show that the copper atom is coordinated by two inequivalent histidine imidazoles. The new Cu(II) material exhibits catalytic activity for DTBQ formation in the presence of dioxygen, with considerable turnover rates and yields. In addition it is highly recyclable and shows high specific surface area.

Expression, characterisation and immunoassay of recombinant marmoset chorionic gonadotrophin dimer and beta-subunit.

A specific and sensitive ELISA for measuring marmoset chorionic gonadotrophin (mCG) in culture medium, urine and plasma was developed using a polyclonal antibody raised against recombinant mCG, tagged with six histidine molecules (rmCG-6His), as the capture antibody. A well-characterised monoclonal antibody (518B7), which was generated against bovine luteinising hormone (bLH) and has been shown to detect CG and LH in Callithrichid monkeys, was biotinylated and used as the secondary antibody. Purified rmCG, calibrated against human CG (hCG; CR127) by bioassay, or the beta-subunit (rmCGbeta), quantified from amino acid analysis and carbohydrate analysis, was used as the standard. The assay was able to detect CG activity in medium collected from cultured marmoset embryos before attachment and through to the trophoblastic vesicle stage, plasma and urine collected from pregnant marmosets, marmoset placenta and pituitary homogenates. The assay was validated and its performance compared with a bioassay based on MA10 cell response to CG, with hCG as the standard. The sensitivity was 103 pg/ml (5 pg/well) of rmCGbeta and 476 pg/ml (24 pg/well) of the heterodimer rmCG. The mean recovery of standard added to embryo culture medium, marmoset urine and plasma was 104, 112 and 92% respectively. The intra- and interassay variation was less than 10 and 16% respectively. The low cross-reactivity with cynomolgus monkey and baboon LH, their beta-subunits, cynomolgus monkey and baboon follicle-stimulating hormone and hCG suggests that the assay is specific for mCG.

INDO Study on the Comparison of the Nonbonded Environments of QI (QA) and QII (QB) in PSU

INDO studies have been carried out for the elucidation of the difference in the nonbonded polarizable environment of QI (QA) and QII (QB) in thylakoid discs in chloroplast (in bacteria). The free energy of reduction of QII by QI- (-0.13 eV in vivo) has been explained by considering a more polar environment for QI. Three environmental features have been accommodated. Each plastoquinone is hydrogen bonded to the imidazole ring of a histidine molecule that serves as the most proximate environment. The RC protein surrounding the plastoquinone has been viewed as a dielectric continuum. As the most logical way of accounting for the difference in the protein environment of QI and QII, two additional peptide fragments have been symmetrically placed on the two sides of the plastoquinone ring plane of QI. Our calculation indicates that the protein environment is closer to QI than to QII. The proximity indicates that QI must be tightly bound as its escape would be prohibited by steric effect, and QII would be held m...

Model Molecules for the Active Centre of Alcoholdehydrogenases—An FT-IR Study

We synthesized a triamide of Kemp's acid with two cysteine groups and one histidine group (compound 1), and a triamide of 1,3,5-pentane tricarboxylic acid with tyrosine, histidine, and arginine molecules (compound 2). From compound 1 we obtained the hydrated Zn2+complex, compound 3. The FT-IR spectra of various complexes of compounds 1–3 with NAD+show no IR continua and hence, no hydrogen-bonded chains with proton polarizability are present. In the case of the complex (compounds 2 and 3 and NAD+) an intense continuum demonstrates that a hydrogen-bonded chain is formed with large proton polarizability due to collective proton motion. This proton pathway is discussed. The O atom of the nicotinamide group of NAD+is a strong hydrogen bond acceptor. This result is discussed with regard to the catalytic mechanism.

X-ray studies on crystalline complexes involving amino acids and peptides. XXXI. Effect of chirality on ionization state, stoichiometry and aggregation in the complexes of oxalic acid with L- and DL-histidine.

Crystals of the oxalic acid complex of L-histidine (orthorhombic P2(1)2(1)2(1); a = 5.535(4), b = 6.809(4), c = 26.878(3) A; R = 3.6% for 1188 observed reflections) contain histidine molecules and semi-oxalate ions in the 1:1 ratio, while the ratio is 1:2 in the crystals of the DL-histidine complex (monoclinic P2(1)lc; a = 6.750(7), b = 10.139(2), c = 19.352(2) A, beta = 90.8 degrees; R = 3.7% for 3176 observed reflections). The histidine molecule in the latter has an unusual ionization state with positively charged amino and imidazole groups and a neutral carboxyl group. The molecule has the sterically least favourable allowed conformation with the side chain imidazole ring staggered between the alpha-amino and the alpha- carboxyl (carboxylate) groups, in both the structures. The unlike molecules aggregate into separate alternating layers in both of them. There are elements of similarity in the aggregation patterns in the semi-oxalate layers in the two complexes, but the patterns in the amino acid layers are entirely different. Interestingly, the crystal structure of L-histidine semi-oxalate has broad similarities with that of DL-histidine = glycolate, demonstrating how broad features of aggregation could be retained inspite of changes in chirality and composition. The unusual ionization state of the amino acid molecule in the DL-histidine complex is reflected in a hitherto unobserved aggregation pattern in its crystal structure.

Reactions of the cis-diamminediaquaplatinum (II) cation with histidine and related molecules

The reaction of cis-[Pt(NH 3) 2(H 2O) 2] 2+ ( 1) with histidine (H 3his +) at pH 2–3 gave initially complexes with histidine bound through carboxylate only, then, after standing, the complex containing an amine nitrogen (N A), carboxylate oxygen-chelate ring [Pt(NH 3) 2(H 2-his- N A , O)] 2+. Increasing the pH to 8–9 caused loss of one imidazole proton, followed by isomerization to the species with a imidazole N(3), N A-chelate ring, [Pt(NH 3) 2(Hhis- N A ,N(3))]. From the variation of NMR parameters with pH, p K a for loss of the last imidazole proton was determined (11.2 ± 0.1). Histidine methyl ester and histidinamide each reacted slowly with 1 at pH 5.5 to give the N A , N(3)-chelate complex. With N-(histidyl)glycine the initial complexes at pH 5 contained the ligand bound only through carboxylate, but a N A , N(3)-chelate complex then formed. With an excess of 1, a second diammineplatinum moiety was bound, initially through the free carboxylate, then chelated by carboxylate and peptide nitrogen. With N-acetylhistidine and N-( β-alanyl)histidine at pH 4–5, the initial complexes also contained carboxylate-bound ligands, then a chelate ring was formed involving carboxylate and the deprotonated amide or peptide nitrogen, N A. With N-(glycyl)histidine, more complex reactions involving the terminal nitrogen atom also occurred. In alkaline solution, these N A , O-chelate complexes reacted slowly to form a dinuclear complex with one ligand bound to one Pt atom through N A and N(3), and to the second platinum through N(1) of bridging imidazolate. The second ligand was bound monodentate to the second platinum through N A.

Generation of nitric oxide from S-nitrosothiols using protein-bound Cu 2+ sources

We have recently shown that S-nitrosothiols (RSNOs) decompose in aqueous buffer to give nitric oxide, an important signalling molecule, and the corresponding disulphides. This occurs by reaction with Cu+ generated from Cu2+ (supplied as hydrated Cu2+) by thiolate reduction. To establish whether these reactions are feasible in vivo, we set out to determine whether Cu2+ bound to an amino acid, a tripeptide or to human serum albumin (HSA) could serve as a Cu+ source for generation of NO from S-nitrosothiols. Experiments with Cu2+ bound to the tripeptide Gly-Gly-His or to two histidine molecules or to HSA showed that Cu+ was released (and trapped with neocuproine) when the copper source was treated with a thiol at pH 7.4. RSNO decomposition was achieved with all three copper sources, although not as rapidly as with added hydrated Cu2+. Decomposition was also catalyzed by ceruloplasmin. These results show clearly that amino-acid- and protein-bound Cu2+ can be reduced by thiolate ion to Cu+, which will generate NO from RSNO species, thus providing a realistic model for these reactions in vivo.

Mechanism of cyanogenesis: the crystal structure of hydroxynitrile lyase from Hevea brasiliensis

Background: Over three thousand species of plants, including important food crops such as cassava, use cyanogenesis, the liberation of HCN upon tissue damage, as a defense against predation. Detoxification of cyanogenic food crops requires disruption of the cyanogenic pathway. Hydroxynitrile lyase is one of the key enzymes in cyanogenesis, catalyzing the decomposition of an acyanohydrin to form HCN plus the corresponding aldehyde or ketone. These enzymes are also of potential utility for industrial syntheses of optically pure chiral cyanohydrins, being used to catalyze the reverse reaction. We set out to gain insight into the catalytic mechanism of this important class of enzymes by determining the three-dimensional structure of hydroxynitrile lyase from the rubber tree, Hevea brasiliensis. Results The crystal structure of the enzyme has been determined to 1.9 Å resolution. It belongs to the α/ β hydrolase superfamily, with an active site that is deeply buried within the protein and connected to the outside by a narrow tunnel. The catalytic triad is made up of Ser80, His235 and Asp207. By analogy with known mechanisms of other members of this superfamily, catalysis should involve an oxyanion hole formed by the main chain NH of Cys81 and the side chains of Cys81 and Thr11. Density attributed to a histidine molecule or ion is found in the active site. Conclusion By analogy with other α/ β hydrolases, the reaction catalyzed by hydroxynitrile lyase involves a tetrahedral hemiketal or hemiacetal intermediate formed by nucleophilic attack of Ser80 on the substrate, stabilized by the oxyanion hole. The SH group of Cys81 is probably involved in proton transfer between the HCN and the hydroxynitrile OH. This mechanism is significantly different from the corresponding uncatalyzed solution reaction.

Crystal and molecular structure of L-(+)-histidine acetate dihydrate (at 123K)

Abstract Single crystals of L-(+)-histidine acetate dihydrate were obtained from an aqueous solution containing L-histidine and acetic acid. The crystals are triclinic with the cell dimensions, a = 8.519(3) Å, b = 9.056(4) Å, c = 9.026(3) Å, α = 61.72(3)°, β = 86.63(3)°, γ = 86.26(3)°, space group = P1 and Z = 2. Intensities of 4725 reflections (MoK α were collected (at 123 K) using an automated four-circle diffractometer. The structure was solved using direct methods and refined to a final R index of 0.039 and Rw index of 0.048 for 4423 reflections with intensities larger than 3σ(I). Histidine acetate exists in the crystals as a salt where the proton from acetic acid is transfered to the imidazole ring whereas the carboxylic group is left unprotonized. The geometry of the two independent histidine molecules is nearly identical. There is an extensive system of hydrogen bonds stabilizing the structure.

Crystal and molecular structure of L-(S)-histidine dihydrochloride (monoclinic form)

Abstract Single crystals of L-histidine dihydrochloride were obtained from an aqueous solution containing L-histidine and diluted hydrochloric acid. The crystals are monoclinic with the cell dimensions, a = 5.243(2) Å, b = 7.257(1) Å, c = 13.350(1) Å, β = 92.65(1)°, space group P21, and Z = 2. Least-squares refinement using 2685 X-ray (MoK α ) reflections has led to an R factor of 0.029. The L-histidine moiety in this complex exists as a dication where the carboxylic group as well as the amino nitrogen and the imidazole ring are protonated. Based on the N–Cα–Cβ–Cγ torsion angle (ψ ⊥ = 57.1°), the conformation of the histidine molecule in this structure is g+, whereas the conformation in the orthorhombic form of this complex (reported earlier) is g−. There are no direct contacts (hydrogen bonds) between the histidine moieties as all the intermolecular bonding seem to involve Cl− ions.

The Crystal Structure of benzoyl – histidine monohydrate

Abstract The crystal structure of benzoyl-histidine monohydrate (BYLH hereafter), C13H12N3O3 · H2O was determined from three dimensional data of 3012 independent reflections measured on a Enraf-Nonius (CAD4) single crystal diffractometer. The compound crystallizes in the orthorhombic space group P212121 with cell dimensions α = 7.102(1) Å, β = 13.783(3) Å, c = 14.160(4) Å, V = 1385.92 Å3, F.W. = 277.28, F(000) = 584 ϱ calc = 1.32 g cm−3 and Z = 4. The structure was solved with direct methods. All positional and anisotropic thermal parameters were refined by full-matrix least-squares calculations. The final reliability factor was R = 0.040, while the weighted one was Rw = 0.034. The H atoms found in the difference Fourier map were refined isotropically. The compound consists of a histidine molecule bound to a benzoyl group. There is also a cocrystallized water molecule stabilized through a hydrogen bridge. The 5-membered ring of the histidine has its tautomeric form, after the transfer of the H atom from the N δ to the N ε atom of the ring. There is an sp2 conformation around C6 while the conformation around C3 is that of sp3. The histidine ring forms with the benzene ring a dihedral angle of 109.8(1)°. All angle values and bond distances agree very well with the expected values in the literature.

X‐Ray studies on crystalline complexes involving a mino acids and peptides

L-Histidine acetate crystallizes in two forms: (I) orthorhombic; P2(1)2(1)2(1); a = 5.027, b = 11.126, c = 17.473 A; Z = 4; (II) monoclinic; C2; a = 15.649, b = 9.276, c = 8.566 A; beta = 94.65 degrees; Z = 4. The structures were solved by direct methods and refined to R-values of 0.056 and 0.089 for 1131 and 1330 observed reflections, respectively. The conformations of the histidine molecule in the two forms are different. However, both are such that they facilitate the occurrence of a specific interaction of the histidine molecule with a carboxylate group. The basic elements of aggregation are hydrogen-bonded histidine ribbons, but they are of different types in the two structures. The ribbons are interconnected by acetate ions to form the crystals. The structures contain two characteristic interaction patterns involving amino and carboxylate groups, one of which is observed for the first time. The two water molecules in form II and their symmetry equivalents form an uninterrupted hydrogen-bonded chain running through the crystal. They also present an interesting case of disorder in hydrogen bonds. A comparative study involving amino acid complexes of acetic acid shows that the presence of acetate ion could lead to new aggregation patterns, specific interactions and characteristic interaction patterns with varying degrees of similarity with those observed in other structures containing amino acids.

X‐ray studies on crystalline complexes involving amino acids and peptides. XXIV. Different ionization states and novel aggregation patterns in the complexes of succinic acid with DL‐and L‐histidine

AbstractDiffusion of acetonitrile into an aqueous solution of DL‐histidine and succinic acid in 1:3 molar proportions results in the crystals of DL‐histidine hemisuccinate dihydrate [triclinic, P1, a = 7.654(1), b = 8.723(1), c = 9.260(1) Å, α = 77.23(1), β = 72.37(1) and γ = 82.32 (1)°]. The replacement of DL‐histidine by L‐histidine in the crystallization experiment under identical conditions leads to crystals of L‐histidine semisuccinate trihydrate [orthorhombic, P212121, a = 7.030 (1), b = 8.773 (1), and c = 24.332 (3) Å]. The structures were solved using counter data and refined to R values of 0.056 and 0.054 for 2356 and 1778 observed reflections, respectively. Histidine molecules in both the complexes exist in open conformation I. Succinate and semisuccinate ions in them are planar, and exactly or nearly centrosymmetric. In the DL‐histidine complex, the amino acid molecules form double ribbons and the succinate ions occupy voids left behind when the double ribbons aggregate, as in inclusion compounds. In the L‐histidine complex, the amino acid molecules form columns; so do the semisuccinate ions and water molecules. The two columns interdigitate to form the complex crystal. There are similarities between the molecular aggregation in the complexes and that in the crystals of L‐ and DL‐histidine. However, the presence of succinic acid has the effect of disrupting, partially or totally, head‐to‐tail sequences involving amino acid molecules. © 1993 John Wiley & Sons, Inc.

Histidyl conformations and short N–H...N hydrogen bonds: Structure of D,L-histidyl-L,D-histidine pentahydrate

D,L-Histidyl-L,D-histidine pentahydrate, C12H16-N6O3.5H2O, Mr = 382.38, F(000) = 408, crystallizes in the monoclinic space group Pc with the cell dimensions a = 9.971 (2), b = 4.745 (2), c = 19.572 (3) A and beta = 96.08 (1) degree, V = 920.6 A3, Z = 2, D chi = 1.379 g cm-3. mu = 1.083 cm-1, T = 295 K, Mo K alpha, lambda = 0.71073 A. Final R (on F) = 0.040 for 1658 observed reflections with I greater than or equal to 3 sigma (I). This dipeptide crystallizes in a zwitterionic form with protonation of the C-terminal imidazole ring. Both histidine units exist in the g+ or 'closed' conformation with C alpha-C beta torsion angles of 67.2 (3) and 63.6 (3) degrees. Principal torsion angles, omega = 176.8 (2). psi 1 = 161.8 (3) and phi 2 = -152.1 (3) degrees, are indicative of a highly extended trans conformation. Intramolecular hydrogen bonding occurs between the imidazole rings [N2D-H2D1...N1D = 2.724 (4) A]. Intermolecular hydrogen bonding occurs between symmetry-related histidine molecules forming chains along the gamma axis and includes another short [2.764 (4) A] N-H...N interaction. The five water molecules occupy channels between adjacent histidine layers.

Structure of diprotonated DL-histidinium dinitrate

C6H11N3O2(2+).2NO3-, M(r) = 281.18, monoclinic, P2(1)/a, a = 8.370 (2), b = 14.973 (3), c = 9.342 (2) angstrom, beta = 100.69 (2)-degrees, V = 1150 (1) angstrom 3, Z = 4, D(m) = 1.622 (flotation), D(x) = 1.623 g cm-3, lambda-(Mo K-alpha) = 0.71073 angstrom, mu = 1.62 cm-1, F(000) = 584, T = 293 K, R = 0.035, wR = 0.037 for 1104 unique reflections with I > 3-sigma-(I). In addition to the usual amino NH3+ group, the carboxylate group and the imidazole ring of the histidine molecule are protonated. Hence this compound is diprotonated. One O atom of one of the nitrate groups is distorted.