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1

Molecular modelling study of the role of cholesterol in the stimulation of the oxytocin receptor.

100%

Politowska E., Kaźmierkiewicz R., Wiegand V., Fahrenholz F., Ciarkowski J.

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2001

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vol. 48

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issue 1

83-93

EN

Cholesterol, an integral component of membranes in Eucaryota, is a modifier of membrane properties. In vivo studies have demonstrated that cholesterol can also modulate activities of some G protein-coupled receptors (GPCRs), which are integral membrane proteins. This can result either from an effect of cholesterol on the membrane fluidity or from specific interactions of the membrane cholesterol with the receptor, as recently demonstrated for the cholecystokinin type β (CCKRβ) or the oxytocin receptor (OTR). Using molecular modelling, we studied conformational preferences of cholesterol and several of its analogues. Subsequently, we simulated the distributions of their preferred conformations around the surface of OTR, CCKRβ and a chimeric oxytocin/cholecystokinin receptor. Consequently, we suggest residues on the surface of OTR which are potentially significant in the OTR/cholesterol interaction.

2

Theoretical studies of binding modes of two covalent inhibitors of cysteine proteases.

86%

Drabik P., Politowska E., Czaplewski C., Kasprzykowski F., Łankiewicz L., Ciarkowski J.

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2000

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vol. 47

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issue 4

1061-1066

EN

Physiological and pathological roles of cysteine proteases make them important targets for inhibitor development. Although highly potent inhibitors of this group of enzymes are known, their major drawback is a lack of sufficient specificity. Two cysteine protease covalent inhibitors, viz. (i) Z-RL-deoxo-V-peptide-epoxysuccinyl hybrid, and (ii) Z-RLVG-methyl-, have been developed and modeled in the catalytic pocket of papain, an archetypal thiol protease. A number of configurations have been generated and relaxed for each system using the AMBER force field. The catalytic pockets S3 and S4 appear rather elusive in view of the observed inhibitors' flexibility. This suggest rather limited chances for the development of selective structure-based inhibitors of thiol proteases, designed to exploit differences in the structure of catalytic pockets of various members of this family.

3

Molecular modeling of the oxytocin receptor/bioligand interactions

85%

Politowska E., Czaplewski C., Ciarkowski J.

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3 Acta Biochimica Polonica

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3 Ciarkowski J.

3 Politowska E.

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1 Drabik P.

1 Fahrenholz F.

1 Kasprzykowski F.

1 Kaźmierkiewicz R.

1 Wiegand V.

1 Łankiewicz L.

Molecular modelling study of the role of cholesterol in the stimulation of the oxytocin receptor.

Theoretical studies of binding modes of two covalent inhibitors of cysteine proteases.

Molecular modeling of the oxytocin receptor/bioligand interactions