Conformational analysis of peptide substrates and inhibitors of the Zn2+ G and serine R61 D-alanyl-D-alanine peptidases

in European Journal of Biochemistry (1981), 121(1), 221-232

The tripeptide Nα,Nɛ-diacetyl-l-lysyl-d-alanyl-d-alanine (Ac2- l-LLys1-dAIa2-dAIa3), which is the standard substrate of the Zn2+ G and serine R61 d-alanyl-d-alanine peptidases, and several ldd tripeptide ... [more ▼]

The tripeptide Nα,Nɛ-diacetyl-l-lysyl-d-alanyl-d-alanine (Ac2- l-LLys1-dAIa2-dAIa3), which is the standard substrate of the Zn2+ G and serine R61 d-alanyl-d-alanine peptidases, and several ldd tripeptide analogues where the size and/or the electrical charge of the side chains at position 1, 2 or 3 have been modified (alterations affecting more than one position at the same time were not investigated) have been submitted to conformational analyses based on both short-range and long-range interactions. Among the many backbone conformers of minimal energy of the øii space that have been characterized, four types of conformers are the most probable ones. Depending on the peptides, these conformers may have varying relative probability P values so that the leader conformer is not always the same, but, in all cases, the sum of their P values is 90% or more. With the Gly1, Gly2 or Gly3 analogues (which encompass a larger conformational space), the above ∑P values are still as high as 35–50%. All the above tripeptides bind to the serine d-alanyl-d-alanine peptidase and with the exception of the Gly3 and Gly2 analogues, to the Zn2+d-alanyl-d-alanine peptidase with virtually the same efficacy, at least within a range of variation of the Km values for the substrates or the Ki values for the inhibitors, which is less than one order of magnitude. Structural variations at position 1, 2 or 3 in the peptides that are compatible with efficient binding are not necessarily compatible with substrate activity, thus converting the modified peptides into competitive inhibitors. In particular, substrate activity requires a long side chain at position 1 in the peptides. Conformational analyses of Ac2-lLys-dAla-dAla show that the main backbone has a tendency to adopt a ring-like shape from which the lLYS side chain protrudes as an extended structure. This latter structure forms with the C-terminal d-alanyl-d-alanine an angle varying between 120° and 180° (depending on the conformers) so that its N-terminal acetyl group is about 1–1.5 nm apart from the scissile amide bond. High turnover numbers (at enzyme saturation) also require a dAla at position 2 with both d-alanyl-d-alanine peptidases and at position 3 in the case of the serine d-alanyl-d-alanine peptidase. Finally, all the conformers of the lAla2 and lAla3 analogues of Ac2-lLys-dAla-dAla fall outside the backbone conformational space that comprises the φiφi angles exhibited by the four types of conformers of the ldd tripeptides. The lAla2 and lAla3 tripeptide analogues do not bind to the serine d-alanyl-d-alanine peptidase (at least at a 10 mM concentration) but they behave as noncompetitive inhibitors of the Zn2+d-alanyl-d-alanine peptidase. [less ▲]

International Directory of Amateur Astronomical Societies - IDAAS 1982

in International Directory of Amateur Astronomical Societies - IDAAS 1982 (1981), iv + 304pp. (1981)

Not Available

Le nouveau né de mère diabétique

Conference given outside the academic context (1981)

Construction et validation d'épreuves destinées à évaluer les connaissances d'élèves de quatrième année primaire sur l'alimentation dans le cadre d'une action menée par la Croix-Rouge de Belgique

Report (1981)

Ontogenic development of steroid 16 alpha-hydroxylase as a tool for the study of the multiplicity of cytochrome P-450.

in European Journal of Biochemistry (1981), 120

1. Activities of progesterone, testosterone, pregnenolone and dehydroepiandrosterone 16 alpha-hydroxylase are undetectable in the fetal rat liver. During the neonatal period, the four enzymic activities ... [more ▼]

1. Activities of progesterone, testosterone, pregnenolone and dehydroepiandrosterone 16 alpha-hydroxylase are undetectable in the fetal rat liver. During the neonatal period, the four enzymic activities increase in parallel to the concentration of cytochrome P-450. Until puberty, they develop similarly in male and female rat livers. From the 40th to the 55th day, the four steroid 16 alpha-hydroxylase activities increase rapidly in the male rat liver. The sexual differentiation of the steroid 16 alpha-hydroxylation observed in adult male and female rats takes place around the 55th day. 2. In the adult rat liver, steroid 16 alpha-hydroxylase is supported by two forms of cytochrome P-450 (form I and form II), which differ in their relative affinities for the various steroid substrates, and by their relative proportions in male and female rat livers. These two forms of cytochrome P-450 are also present in the young male and female rat livers, but are roughly equal in proportion. The transition from the immature to the adult repartition of the two forms occurs during puberty and is correlated with the sexual differentiation of the steroid 16 alpha-hydroxylase activities. 3. During the critical phases of the rat ontogenic development, the in vitro interactions between benzo[a]pyrene and steroids were compared at the level of two rat liver monooxygenases: steroid 16 alpha-hydroxylase and aryl hydrocarbon hydroxylase. (a) In the immature male and female rat livers, progesterone 16 alpha-hydroxylase, and to a lesser extent, pregnenolone 16 alpha-hydroxylase are inhibited by benzo[a]pyrene. Progesterone 16 alpha-hydroxylase is also inhibited by metyrapone. (b) In the young rat, aryl hydrocarbon hydroxylase cannot be inhibited by steroids and appears to be supported by a single form of cytochrome P-450. The transition from the immature to the adult situation occurs around the 40th day. [less ▲]

Infections respiratoires et pathologie de la clairance muco-ciliaire

in Revue Médicale de Liège (1981), 36(20), 760-6

L'ultrastructure et le fonctionnement des cils de la muqueuse respiratoire sont actuellement mieux connus. Il est donc possible de diagnostiquer les dyskinésies ciliaires qui peuvent expliquer l ... [more ▼]

L'ultrastructure et le fonctionnement des cils de la muqueuse respiratoire sont actuellement mieux connus. Il est donc possible de diagnostiquer les dyskinésies ciliaires qui peuvent expliquer l'inefficacité de "l'escalator mucociliaire". [less ▲]

A photoelectric investigation of light variability in Ap stars

in Astronomy and Astrophysics. Supplement Series (1981), 46

A study of the light variability of a number of peculiar A stars, mainly in Stromgren colors u and v and in peculiarity index Delta-a, leads to the proposal of the following light variability periods: (1 ... [more ▼]

A study of the light variability of a number of peculiar A stars, mainly in Stromgren colors u and v and in peculiarity index Delta-a, leads to the proposal of the following light variability periods: (1) HD 5601, 1.11 days; (2) HD 19712, 2.19 days; (3) HD 30849, 15.86 days; (4) HD 38823, 8.64 days; (5) HD 53116, 11.98 or 18.10 days; (6) HD 56022, 0.92 days; and (7) HD 81009, 33.97 days. In addition, evidence is given for variability of HD 94660 on a time scale on the order of months or years, and it is shown that the rotation period proposed by Borra and Landstreet (1980) for HD 25267 is not supported by the light variations observed. The character of Delta-a variability is discussed. [less ▲]

Evaluation of Housing Heat Gains due to Metabolism, Artificial Lighting, Appliances and Domestic Hot Water User

(1981, October)

The evaluation of sensible heat gains due to house occupancy is possible by taking into account the family occupancy pattern, the main source of information that gives up: - the rooms occupied by any ... [more ▼]

The evaluation of sensible heat gains due to house occupancy is possible by taking into account the family occupancy pattern, the main source of information that gives up: - the rooms occupied by any member of the family (with the activity realized at each moment of the day) ; - the use of domestic hot water ; - the use of appliances. Two household occupancy patterns are chose, corresponding to most common families. The calculation of incidental heat gains due to metabolism takes into account radiative and convective exchange from human body to its ambiance. The activities realized along the day are known, and so on the illumination levels. The necessary artificial lighting electrical power and the periods of switching-on are determined with the help of simplified methods. Heat losses wasted at production, storage, distribution and use of domestic hot water are situated. Internal heat gains lost by domestic appliances (gas or electric cooker, refrigerator, deep-freezer…) are estimated taking into account characteristics (volume, size) of appliance and for a typical use. Then internal heat gains due to human occupancy become possible to evaluate hour by hour and room by room, which is interesting for estimation of peak overheating temperature or decrement of consign temperature. [less ▲]

Evaluation of risk using serial laboratory data in acute myocardial infarction

Conference (1981, September)

Formation of P Cygni profiles with limb darkening of the stellar core

in Astrophysics & Space Science (1981), 79

In the framework of the Sobolev approximation, the effects of limb darkening of the stellar core on the formation of line profiles in rapidly expanding envelopes are investigated. For the case of outward ... [more ▼]

In the framework of the Sobolev approximation, the effects of limb darkening of the stellar core on the formation of line profiles in rapidly expanding envelopes are investigated. For the case of outward-accelerating envelopes, it is shown that the P Cygni profiles, calculated with and without limb darkening, do appear almost identical as long as the size of the envelope remains large with respect to the radius of the star. As the extent of the envelope decreases, the resulting profiles are found to differ appreciably close to the line center. When considering outward-decelerating (or equivalently inward-accelerating) envelopes, calculations with the limb darkening effects reveal that the P Cygni profiles are more strongly affected than in the previous case. These effects are specially important in the blue wing and near the center of the resulting line profiles, irrespective of the size of the envelope. [less ▲]