Structural Biology is an increasingly important and exciting area. It encompasses all the range of structural research on biological systems. At the Weizmann Institute, this research is part of the Faculty of Chemistry. The current projects utilize the main methodologies available for biological structural studies, such as X-ray crystallography, NMR, electron microscopy, molecular biology and many others. Modern and sophisticated instrumentational facilities are available, most of which are state-of-the-art. Studies are being performed on the molecular structures and structure-function relationships in biological macromolecules, such as proteins, DNA chains and their complexes, and saccharides. Efforts are directed towards the design of potential drugs. Whole intracellular assemblies and organelles, such as the ribosomes, which contain tens of macromolecules, are being investigated. The powerful techniques of site-directed mutagenesis and thermodynamics are being used to characterize, in detail, the interactions that stabilize proteins and their activity. Antigen-antibody complexes are being studied, by multi-dimensional NMR methods. Biomineralization, ie controlled mineral deposition by organisms to form skeletal tissues is being investigated, from the molecular interactions between proteins and crystals to the ultrastructure and properties of the tissue. Finally, DNA related research includes theoretical and experimental studies on the three-dimensional structure of DNA, and the many hierarchical levels of repetitive structures that are encoded into it.

L. Addadi

Mechanisms of crystal nucleation and modulation of crystal growth and properties in biomineralization (bone, mollusk shells, echinoderms) (L. Addadi, S. Weiner).

Antibodies that recognize crystal surfaces and 2-dimensional organized patterns (L. Addadi).

Mechanism of cell adhesion using crystal substrates (L. Addadi, in collaboration with B. Geiger).

J. Anglister

NMR studies of the principal neutralizing determinant of HIV-1 and its interactions with virus neutralizing antibodies.

NMR studies of Bungarotoxin and its interaction with the acetylcholine receptor.

The three dimensional structure of the extra cellular domain of the receptor for interferon a (in collaboration with Dr. Gideon Schreiber, Dept of Biological Chemistry).

D. Fass

Structures of retrovirus envelope proteins and mechanisms of retrovirus entry into cells.

Structure and function of proteins that modulate intracellular membrane dynamics.

Origins of disulfide bonds for oxidative protein folding.

http://www.weizmann.ac.il/sb/faculty_pages/Fass/home.html

A.J. Gilboa

X-ray crystallographic and thermodynamic investigation of the interaction of saccharides with the protein, concanavalin A (with F. Frolow, Tel Aviv University).

Ultrahigh resolution study of the transition metal-binding site of concanavalin A by means of EPR and cryogenic X-ray crystallography (with D. Goldfarb, Chemical Physics).

Structure of furanosides :High resolution X-ray, neutron diffraction and quantum mechanical studies (with J.M.L. Martin, Organic Chemistry and F. Frolow, Tel Aviv University).

X-ray crystallographic study of bacterial cytochrome b1 (bacterioferritin) (with F. Frolow, Tel Aviv University).

A. Horovitz

Allostery in the structure and function of GroEL and CCT chaperonins.

LFER analysis of allosteric transitions in proteins.

Chaperonin-mediated protein folding.

K.A. Muszkat

CIDNP and NMR studies of proteins: conformations, protein-protein interactions, binding, and protein folding under physiological conditions.

CIDNP and NMR studies of antigenic and immunogenic peptides and their conformations. CIDNP studies of transient conformations of proteins and peptides.

Synthesis of cyclic peptides incorporating Y-E epitopes.

M. Safro

X-ray analysis of phenylalanyl-tRNA synthetase from Th. Thermophilus and its complexes with functional ligands: tRNA, PheAMP, etc.

Human phenylalanyl-tRNA synthetase: cloning, expression, 3-D-structure, drug-design.

Crystal structure of cytoskeletal proteins: vinculin, E-cadherin (in collaboration with B. Geiger).

I. Sagi

Structural -Dynamic studies of Metalloenzymes .and Protein-Nucleic Acid Interactions

Our research covers a wide range of areas with the common themes of dynamic structure-function investigations. The principle areas of investigation are mechanism of action of metalloenzymes and protein-nucleic acid interactions. Our objective is to study the mechanism of catalysis by direct structural determination of the competent intermediates that evolve in the course of reaction in real time. We study the reaction mechanism of these enzymes by developing and using molecular biology, protein chemistry, X-ray spectroscopy, and microscopy. Our biophysical and X-ray methods are modified for following dynamical changes in enzymes and nucleic acids that are taking place during the course of reaction. Ongoing projects include: (1) Mechanism of catalysis and inhibition of metalloproteinases (MMPs) and alcohol dehydrogenase. (2) Protein-nucleic acid interactions of RNA/DNA helicases.

Z. Shakked

X-ray and solution studies of DNA oligomers.

Structural and biochemical studies of proteins involved in transcriptional regulation.

J.L. Sussman

X-ray structural analysis and molecular biology studies on proteins from the nervous system, including acetylcholinesterase (AChE), human, torpedo, drosophila, and krait; butyrylcholinesterase; neural cell adhesion proteins with sequence similarity to AChE; and paraoxonase.

Structure based drug design studies on AChE and beta-secretase, including studies of complexes with transition state analogs; potential drugs for the treatment of Alzheimer's disease; and snake neurotoxins.

3D structural studies of halotolerant proteins from unicellular alga Dunaliella.

Application of ultra rapid X-ray diffraction methods to study the enzymatic mechanism of AChE in real time.

3-D structure analysis and prediction of protein structures; and design and construction of a large object oriented relational data base for 3D structures of biological macromolecules found in the protein data bank.

E.N. Trifonov

Origin and evolution of the genetic code.

Loop fold structure of proteins (with I. Berezovsky).

Evolution of protein structure (with I. Berezovsky).

S. Weiner

Biomineralization: mechanisms of mineral formation and growth in biology (L. Addadi and S.Weiner).

Structure - mechanical function relations in mineralized tissues (bone and teeth) (S. Weiner and H.D. Wagner).

Archaeological science: minerals and molecules in the sediments of the archaeological record.

A. Yonath

Ribosomes: structure analysis by X-ray crystallography.

Antibiotics of protein biosynthesis.

Molecular Genetics and biochemistry of ribosomal RNA and proteins.