Search results

Sort By:

Limit search:

Theoretical models of catalytic domains of protein phosphatases 1 and 2A with Zn2+ and Mn2+ metal dications and putative bioligands in their catalytic centers.

100%

Woźniak-Celmer E., Ołdziej S., Ciarkowski J.

2001

vol. 48

issue 1

35-52

The oligomeric metalloenzymes protein phosphatases dephosphorylate OH groups of Ser/Thr or Tyr residues of proteins whose actions depend on the phosphorus signal. The catalytic units of Ser/Thr protein phosphatases 1, 2A and 2B (PP1c, PP2Ac and PP2Bc, respectively), which exhibit about 45% sequence similarity, have their active centers practically identical. This feature strongly suggests that the unknown structure of PP2Ac could be successfully homology-modeled from the known structures of PP1c and/or PP2Bc. Initially, a theoretical model of PP1c was built, including a phosphate and a metal dication in its catalytic site. The latter was modeled, together with a structural hydroxyl anion, as a triangular pseudo-molecule (Zno or Mno), composed of two metal cations (double Zn2+ or Mn2+, respectively) and the OH- group. To the free PP1c two inhibitor sequences R29RRRPpTPAMLFR40 of DARPP-32 and R30RRRPpTPATLVLT42 of Inhibitor-1, and two putative substrate sequences LRRApSVA and QRRQRKpRRTI were subsequently docked. In the next step, a free PP2Ac model was built via homology re-modeling of the PP1c template and the same four sequences were docked to it. Thus, together, 20 starting model complexes were built, allowing for combination of the Zno and Mno pseudo-molecules, free enzymes and the peptide ligands docked in the catalytic sites of PP1c and PP2Ac. All models were subsequently subjected to 250-300 ps molecular dynamics using the AMBER 5.0 program. The equilibrated trajectories of the final 50 ps were taken for further analyses. The theoretical models of PP1c complexes, irrespective of the dication type, exhibited increased mobilities in the following residue ranges: 195-200, 273-278, 287-209 for the inhibitor sequences and 21-25, 194-200, 222-227, 261, 299-302 for the substrate sequences. Paradoxically, the analogous PP2Ac models appeared much more stable in similar simulations, since only their "prosegment" residues 6-10 and 14-18 exhibited an increased mobility in the inhibitor complexes while no areas of increased mobility were found in the substrate complexes. Another general observation was that the complexes with Mn dications were more stable than those with Zn dications for both PP1c and PP2Ac units.

Design of a knowledge-based force field for off-lattice simulations of protein structure

88%

Liwo A., Ołdziej S., Kaźmierkiewicz R., Groth M., Czaplewski C.

Acta Biochimica Polonica

1997

vol. 44

issue 3

527-547

Effect of tetrazole moiety on coordinating efficiency of deltorphin.

76%

Łodyga-Chruścińska E., Ołdziej S., Micera G., Sanna D., Chruściński L., Olczak J., Zabrocki J.

vol. 51

issue 1

93-106

A study of the effect of the tetrazole moiety, a cis-amide bond surrogate, on the Cu(II) coordinating properties of oligopeptides is reported. Insertion of the tetrazole moiety Ψ[CN4] into the peptide sequence of [D-Ala2]deltorphin I changes considerably the coordination ability of the peptide. Potentiometric and spectroscopic results show that if the tetrazole moiety is in a suitable position in the peptide chain, i.e. it follows the second residue, a stable CuL species involving 3N coordination is formed in the physiological pH range. The tetrazole Ψ[CN4] ring provides one of these nitrogens. The data indicate that Cu(II) ions are strongly trapped inside a bent peptide backbone. The peptide conformation changes achieved by Cu(II) coordination may be essential for the binding of tetrazole deltorphins at opiate receptors.

Refine search results

3 Acta Biochimica Polonica

1 2004

1 2001

1 1997

3 Ołdziej S.

1 Chruściński L.

1 Ciarkowski J.

1 Czaplewski C.

1 Groth M.

1 Kaźmierkiewicz R.

1 Liwo A.

1 Micera G.

1 Olczak J.

1 Sanna D.

1 Woźniak-Celmer E.

1 Zabrocki J.

1 Łodyga-Chruścińska E.

Search results

Theoretical models of catalytic domains of protein phosphatases 1 and 2A with Zn2+ and Mn2+ metal dications and putative bioligands in their catalytic centers.

Design of a knowledge-based force field for off-lattice simulations of protein structure

Effect of tetrazole moiety on coordinating efficiency of deltorphin.