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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was shown that ferrocytochrome P450 forms a nonequilibrium state if ferrocytochrome P450 and its complexes are reduced in freezed water-glycerol solutions by thermolysed electrons, arising during gamma-radiolysis of the matrix at 77 degrees K. Unlike the equilibrium form of ferrocytochrome P450 with the heme iron at the high-spin state the reduced nonequilibrium form of the protein contains the heme iron at a low-spin state. The absorption spectrum of ferrocytochrome P450 in the nonequilibrium state is characterized by alpha and beta-bands at 562 and 534 nm, respectively, whereas the magnetic circular dichroism spectra exhibit type A effect at 562 nm. Upon temperature increasing the nonequilibrium state is relaxed to the equilibrium one. Type 1 substrates had practically no influence on the spectral characteristic of the nonequilibrium form of ferrocytochrome P450. Binding of type 2 substrates results in an essential decrease of the intensity ratio of the alpha- and beta-bands (A alpha/A beta) and is accompanied by a red-shift of the alpha-band and corresponding magnetic circular dichroism effect. It was shown that mercaptoethanol complex of hemoglobin, formed by reduction at 77 degrees K is spectrally similar to the nonequilibrium ferrocytochrome P450 complex with type 2 substrates. From analysis of experimental data one can conclude that (i) the ligand environment of heme iron in oxidased and reduced cytochrome P450 are different; (ii) the sixth axial ligand of the heme iron in the oxidised protein is probably a water molecule (OH-) attached by a hydrogen bond to the neighbouring histidine. It is assumed that a similar nonequilibrium form of cytochrome P450 can be formed in physiological conditions.
Mol Biol (Mosk)
PMID:[Absorption and magnetic circular dichroism spectra of hemoproteins in nonequilibrium states. V. Cytochrome P450 and its substrate complex]. 54 82

The kinetic of 1H leads to 3H exchange between water and C(8)H-groups of the guanylic residues in poly(G) . poly(C) and poly(dG) . poly(dC) was investigated within the temperature range from 30 to 90 degrees in 0.5 M NaCl (pH 7.2). It was shown that the exchange in freshly dissolved preparations at temperatures lower than 50 degrees proceeds faster than that in the case of GMP. According to the ylide mechanism of the exchange reaction the observed acceleration of the exchange is considered as a consequence of associates formation in poly(G) . poly(c) and poly(dG) . poly(dC) solutions at temperatures lower than 50 degrees. Associates are stabilized by intermolecular hydrogen bonds in which N(7) atoms of guanylic residues take part. The increase of the temperature is accompanied by gradual disappearance of the exchange acceleration. The retardation of exchange, which is characteristic of most non-associated double-stranded polynucleotides and nucleic acids is observed at the temperatures above 60 degrees. The retardation points to thermal destruction of the associates at temperatures higher than 50 degrees. The associates which are characterized by ordered structure including several "side by side" arranged double-stranded molecules were observed by electron microscopy. The addition of EDTA to solutions as well as the increase of temperature leads to destruction of the associates whereas the addition of Mg2+ makes the associates more stable.
Mol Biol (Mosk)
PMID:[Study of the intermolecular association of poly(G).poly(c) and poly(dG).poly(dC) in solutions by methods of 1H to 3H exchange and electron microscopy]. 54 80

The three-dimensional crystal structure of bovine trypsinogen at approximately pH 7.5 was initially solved at 2.6 A resolution using the multiple isomorphous replacement method. Preliminary refinement cycles of the atomic coordinates trypsinogen have been carried out first to a resolution of 2.1 A, and later to 1.9 A, using constrained difference Fourier refinement; During the process, structure factors Fc and phi c were calculated from the trypsinogen structure and final interpretation was based on an electron-density map computed with terms (2 Fo - Fc) and phases phic at a resolution of 1.9 A. Crystals of trypsinogen grown from ethanol-water mixtures are trigonal with space group P3121, and cell dimension a = 55.17 A and c = 109.25 A. The structure is compared with the bovine diisopropylphosphoryltrypsin structure at approximately pH 7.2, oirginally determined from orthohombic crystals by Stroud et al. (Stroud, R.M., Kay L.M., and Dickerson, R.E. (1971), Cold Spring Harbor Symp. Quant. Biol. 36, 125-140; Stroud, R.M., Kay, L.M., and Dickerson, R.E. (1974), J. Mol. Biol. 83, 185-208), and later refined at 1.5 A resolution by Chambers and Stroud (Chambers, J.L., and Stroud, R.M. (1976), Acta Crystallogr. (in press)). At lower pH, 4.0-5.5 diogen, with cell dimensions a = 55.05 A and c = 109.45 A. This finding was used in the solution of the six trypsinogen heavy-atom derivatives prior to isomorphous phase analysis, and as a further basis of comparison between trypsinogen and the low pH trypsin structure. There are small differences between the two diisopropylphosphoryltrypsin structures. Bovine trypsinogen has a large and accessible cavity at the site where the native enzyme binds specific side chains of a substrate. The conformation and stability of the binding site differ from that found in trypsin at approximately pH 7.5, and from that in the low pH form of diisopropylphosphoryltrypsin. The catalytic site containing Asp-102, His-57, and Ser-195 is similar to that found in trypsin and contains a similar hydrogen-bounded network. The carboxyl group of Asp-194, which is salt bridged to the amino terminal of Ile-16 in native trypsin or other serine proteases, is apparently hydrogen bonded to internal solvent molecules in a loosely organized part of the zymogen structure. The unusually charged N-terminal hexapeptide of trypsinogen, whose removal leads to activation of the zymogen, lies on the outside surface of the molecule. There are significant structural changes which accompany activation in neighboring regions, which include residues 142-152, 215-550, 188A-195. The NH group of Gly-193, normally involved in stabilization of reaction intermediates (Steitz, T.A., Henderson, R., and Blow, D.M. (1969), J. Mol. Biol. 46, 337-348; Henderson, R. (1970), J. Mol. Biol. 54, 341-354; robertus, J.D., Kraut, J., Alden, R.A., and Birkoft, J.J. (1972), Biochemistry 11, 4293-4303) in the enzyme, is moved 1.9 A away from its position in trypsin...
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PMID:Structure of bovine trypsinogen at 1.9 A resolution. 55 51

Theoretical studies on glycyl-alanyl and seryl dipeptides were performed to determine the probable backbone and side-group conformations that are preferred for solvent interaction. By following the method of Lee & Richards [(1971) J. Mol. Biol. 55, 379-400], a solute molecule is represented by a set of interlocking spheres of appropriate van der Waals radii assigned to each atom, and a solvent (water) molecule is rolled along the envelope of the van der Waals surface, and the surface accessible to the solvent molecule, and hence the solvent accessibility for a particular conformation of the solute molecule, is computed. From the calculated solvent accessibilities for various conformations, solvation maps for dipeptides were constructed. These solvation maps suggest that the backbone polar atoms could interact with solvent molecules selectively, depending on the backbone conformation. A conformation in the right-handed bridge (zetaR) region is favoured for both solvent interaction and intrachain hydrogen-bonding. Also the backbone side-chain hydrogen-bonding within the same dipeptide fragment in proteins is less favoured than hydrogen-bonding between side chain and water and between side chain and atoms of other residues. Solvent accessibilities suggest that very short distorted alphaR-helical and extended-structural parts may be stabilized via solvent interaction, and this could easily be possible at the surface of the protein molecules, in agreement with protein-crystal data.
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PMID:Solvent accessibilities in glycyl, alanyl and seryl dipeptides. 58 49

1. Pulmonary and systemic haemodynamics during repeated exercise were studied in 28 patients with chronic lung disease of various etiology, 16 of whom suffered from chronic bronchitis. They performed a moderate exercise repeated after a 20 min rest period. Ventilatory variables, blood gas tensions, cardiac output and vascular pressures (right ventricular end-diastolic, pulmonary arterial, wedge and systemic arterial) were measured at rest, during exercise and again at rest and during the same exercise. 2. Ventilation and blood gas tensions were similar during the two rest and exercise periods; there was, however, a slightly significant difference in oxygen consumption and hydrogen ion concentration between the first and the second exercise period. Pulmonary arterial and wedge pressures were lower during the second rest and exercise, right ventricular filling pressure was lower at rest, and systemic arterial pressure during the second exercise. Cardiac output and pulmonary vascular resistance were unchanged. 3. Changes in systemic arterial pressure were significantly different in a group of patients with arterial oxygen desaturation or perfusion defects, compared with those patients without such impairment.
Clin Sci Mol Med 1978 Nov
PMID:Haemodynamic variables during repeated exercise in chronic lung disease. 72 2

Kinetic aspects of enzymatic reactions proceeding in the autocatalytic mode are considered. Kinetic analysis of a mechanism with proenzyme-enzyme interaction and of mechanism in which activation involves an interaction with the product of enzymatic reaction is presented. It is shown that these mechanisms are distinguished by the dependences of kinetics of the process on enzyme and substrate concentrations. Method is developed for the determination of concentration of active centers of enzyme in the case of activation by reaction product. Conclusions obtained are illustrated using autocatalytic enzymatic systems such as trypsin-trypsinogen and bacterial hydrogenases-hydrogen-4,4'-dimethylbipyridinium.
Mol Biol (Mosk)
PMID:[Autocatalytic enzyme reactions]. 75 85

The concept of an enzyme active site as of an integrated network system, which is substantiated by multipoint contacts between constituents, is presented. The conformational and electronic state of an enzyme active site supposed to be determined by hydrogen bonds network, which connects different subsites and components of the active site. The substrate specificity of an enzyme is achieved by means of hydrogen bonds formation between the protein and nonreacting fragment of the substrate molecule. As a consequence, reacting fragment of a substrate and those of an enzyme are locked in the configuration close to that of the transition state for the reaction. Stereochemical and dynamical aspects of ribonucleases specificity are considered in the framework of the concept. A molecular mechanism for the enzyme-substrate recognition is suggested.
Mol Biol (Mosk)
PMID:[Active sites of enzymes: stereochemistry and dynamics]. 80 80

1. The PCO2 gradient between alkaline urine and arterial blood (U-B PCO2) is thought to depend primarily on distal hydrogen ion secretion. However, other variables affecting the U-B PCO2 include the urine flow rate, the urinary bicarbonate and phosphate excretion rates and the glomerular filtration rate. 2. In order to evaluate the effects of acute changes in these factors on the U-B PCO2, bicarbonate-loaded dogs with maximal U-B PCO2 values were subjected to either acute unilateral elevations of ureteral pressure or hypotension caused by nitroprusside infusion. The results demonstrate that acute reduction in the glomerular filtration rate does not cause a decrease in the U-B PCO2 as long as the urinary concentrations of phosphate and bicarbonate do not decline. 3. Urinary concentrations of phosphate and bicarbonate appeared more important than their excretion rates in the maintenance of elevated U-B PCO2 values.
Clin Sci Mol Med 1977 Feb
PMID:Lack of dependence of urine PCO2 upon reduction of glomerular filtration rate in alkalotic dogs. 84 45

In terms of the mechanical model of molecules, a calculation has been carried out of possible positions and binding energies of 1-methyl uracyl in the contact region of the ribonuclease S active site. In the most preferential orientation, 1-methyl uracyl forms hydrogen bonds C(2)=O(uracyl)...H-N(Thr-45), N-H...Ogamma (Thr-45), C(4)=O... ...H-Ogamma (Ser-123). The base position found (atom coordinates are given) is in complete qualitative agreement with the position of the uracyl in UpcA bound to ribonuclease S as revealed by X-ray analysis. The influence studied of methyl substitution in positions 3 and 5 of the pyrimidine cycle on the base orientation within the protein field. It has been shown that the formation of hydrogen bonds with Thr-45 and Ser-123 is not prerequisite for productive fixation of the phosphoribosyl nucleotide moiety in the catalytic region of the enzyme active site.
Mol Biol (Mosk)
PMID:[A theoretical analysis of the binding of methyl derivatives of uracil at the contact portion of the active center of ribonuclease S]. 94 May 57

An improved 2.5-A electron density map of chymotrypsinogen was calculated by incorporating heavy-atom anomalous scattering effects and a new model of the molecule was constructed. Phases from x-ray structure factors (R = 0.43) computed from this model were then used in the calculation of another electron density map against which the model was further refined. The catalytic Ser-195 side chain in the new model is in the "down" or "acyl" orientation and its Ogamma atom is in position to form a normal hydrogen bond with Nepsilon2 of His-57. In contrast, the corresponding hydrogen bond in alpha-chymotrypsin (Birktoft, J.J., and Blow, D.M. (1972), J.Mol. Biol. 68, 187) is severely distorted, probably as a consequence of a 1.5-A shift in the relative positions of the two cylindrical folding domains composing most of the molecule. We suggest that this activiation induced distortion of the charge-relay, hydrogen-bonding system plays an important role in the genesis of enzymic activity, in accord with an earlier proposal by Wang concerning the role of bent hydrogen bonds in enzyme catalysis (Wang, J.J. (1970), Proc. Natl. Acad. Sci. U.S.A. 66, 874).
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PMID:A detailed structural comparison between the charge relay system in chymotrypsinogen and in alpha-chymotrypsin. 97 71


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