Structure and Function in Molecular Biology

Chair: Jindrich Hasek, Co-chair: Maria Armenia Carrondo (Portugal)

The microsymposium on “Structure and Function in Molecular Biology”, held during the ECM-18 in Praha, August 15-20, chaired by J.Hasek and M.A.Carrondo had seven oral contributions and 18 poster presentations. Oral presentations were attended by about 60 persons. Stephen Neidle (Institute of Cancer Research, Surrey) presented a short review on DNA types of structures from various characteristic forms of duplexes to three-stranded and four-stranded structures. He emphasized the potential importance of quadruplexes with applications in therapy against cancer. The classification of DNA sequences into groups according to their local curvature characteristics was shown by Sandor Pongor (ICGEB, Trieste). He stressed his view concerning the influence of DNA flexibility on the gene regulation, packing and DNA replication. Bohdan Schneider (J. Heyrovsky Institute of Physical Chemistry, Prague) discussed solvation of DNA. Schneider talk summarized several database studies which had shown that water as well as metal cations preferentially bind into sterically well defined sites around DNA bases and phosphates. The stereochemistry of these hydrophilic binding sites vary in dependence on the DNA conformational type. These stereochemical differences may indeed contribute to specificity of DNA intermolecular interactions because the binding sites are probable markers for binding of other ligands, from gene regulating proteins to antisense drugs. Vivian Cody (H. W. I. Medical Research Institute, Buffalo) reported two non-isomorphous forms of Pneumocystis carnii dihydrofolate reductase, pcDHFR. Analysis of these structures shows a 7 Å shift in the loop near residue 23 from an ”open” pcFA binary structure when compared to the “closed” pcFA/MTX//NADP+/NADPH ternary compound. Also a short helical turn in loop 47 is unwound in the binary FA complex. This study provides the first evidence for ligand induced conformational change in pcDHFR, which may be utilized in drug design. The coordination geometry of 38 internal water molecules in acetylcholinesterase from Torpedo californica were analysed by T. Steiner (Weizmann Institute of Science, Rehovolt). These water molecules are fully conserved in four crystal structures of different inhibitor complexes, allowing interpretation of intermolecular interactions with good confidence. These form hybrid networks of O/N-H..O and C-H..O type, and occasionally also aromatic hydrogen bonds. Simulations methods can be used to obtain information on conformational pathways observed in proteins. J. Sopkova from (Gif-sur-Yvette and LURE-Orsay) used the conjugate peak refinement method (CPR) to look into calcium-induced conformational transition of domain III in annexin V. Solvatation effect corrections were introduced in the calculations and the refinement pathway was observed visually as consisting of four principal phases. The fumarase family of lyases was addressed by V. Zaitsev (CCLRC Daresbury laboratory, Warrington). Crystals structures for both the native and recombinant forms of yeast fumarase from Saccharomices cerevisiae have been described and compared with other members of the fumarase family, showing that the positions of catalytically important residues are roughly similar. Discrepancies, however, are still difficult to rationalize and need higher resolution structures. Several tenths of other newly determined enzyme structures were discussed during the poster session, some of them related to the energy pathway, other to drug design (regulating cholesterol level, neurological symptoms), other to accesibility or stereospecifity of active site after enzyme mutations and the rest was related to protein modification and degradation (analysis of binding modes of the serine proteases, etc.). The conference abstracts are avaiblable in the form of conference proceedings at the address http://krystal.karlov.mff.cuni.cz/ecm/ or as a supplement of the Zeischrift fur Kristallografie. The full texts of the principal contributions will be available in the book form in the first half of 1999. More information is available at the internet address given above.

J. Hasek, Chair (ECM-18 report session E3)