M 2012

MOLECULAR INTERVENTIONS OF PEPTIDES AND SMALL MOLECULES: A STRUCTURAL STUDY.

BATHULA, Sreenivas Reddy

Basic information

Original name

MOLECULAR INTERVENTIONS OF PEPTIDES AND SMALL MOLECULES: A STRUCTURAL STUDY.

Authors

Edition

2012

Other information

Type of outcome

Uspořádání konference

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Central European Institute of Technology
Změněno: 2/5/2012 22:18, Mgr. Sreenivas Reddy Bathula, Ph.D.

Abstract

ORIG EN

V originále

MOLECULAR INTERVENTIONS OF PEPTIDES AND SMALL MOLECULES: A STRUCTURAL STUDY. Bathula SR a, Zidek L a, Vondrasek J b, Chaloupkova R a, Svobodova R a, Sklenar V a. a) National Center for Biomolecular Research, Faculty of Science, Masaryk University, Kotlarska 2, Brno, Czech republic b) Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, , Center for Biomolecules and Complex Molecular Systems, Flemingovo nám. 2, 16610 Prague 6, Czech Republic

In English

A 20 residue Trp-cage miniprotein is an ideal model for experimental studies on protein folding mechanisms and computer simulations involving molecular dynamic studies [1, 2]. The miniprotein consists of an order-promoting [3] alpha-helical part made up of residues mostly involved in fold stabilization and a disorder-promoting [4] poly-proline type II (PPII) helical part with residues involved in Trp burial [5]. A peptide of a reversed sequence (with respect to the original Trp-cage) was investigated in order to test the hypothesis that the Trp-cage fold is invariant to the retro operation. CD spectroscopy showed that the peptide is unstructured in water forms an alpha-helical structure in 30% trifluoroethanol at 2 degree centigrade. Its 3D structure was determined using distance restraints derived from 2D NOSEY spectra. Reversing the direction of the Trp-cage sequence revealed the importance of particular motifs in the Trp-cage fold. Structural analysis of the Trp-cage miniprotein showed how the altered amino-acids arrangement can lead to a different protein fold. [*] References 1 Neidigh JW, Fesinmeyer RM, Prickett KS, Andersen NH, Biochemistry., 2001, 40, 13188-200. 2 Chowdhury S, Lee MC, Xiong G, Duan Y, J Mol Biol, 2003, 28,711-7. 3 Al-Sabah S, Donnelly D, Protein Pept Lett., 2004, 11, 9-14. 4 Dunker AK et.al, Mol Graph Model., 2001, 19, 26-59. 5 Barua B, Lin JC, Williams VD, Kummler P, Neidigh JW, Andersen NH, Protein Eng Des Sel., 2008,21,171-85.