Joel L Sussman

Summary

Affiliation: Weizmann Institute of Science
Country: Israel

Publications

  1. pmc An idea whose time has come
    Lucia Banci
    Genome Biol 8:408. 2007
  2. pmc Proteopedia - a scientific 'wiki' bridging the rift between three-dimensional structure and function of biomacromolecules
    Eran Hodis
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Genome Biol 9:R121. 2008
  3. ncbi request reprint FoldIndex: a simple tool to predict whether a given protein sequence is intrinsically unfolded
    Jaime Prilusky
    Biological Services, Weizmann Institute of Science, Rehovot 76100, Israel
    Bioinformatics 21:3435-8. 2005
  4. ncbi request reprint Complexes of alkylene-linked tacrine dimers with Torpedo californica acetylcholinesterase: Binding of Bis5-tacrine produces a dramatic rearrangement in the active-site gorge
    Edwin H Rydberg
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Med Chem 49:5491-500. 2006
  5. pmc The quaternary structure of amalgam, a Drosophila neuronal adhesion protein, explains its dual adhesion properties
    Tzviya Zeev-Ben-Mordehai
    Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    Biophys J 97:2316-26. 2009
  6. ncbi request reprint The binding site of acetylcholine receptor: from synthetic peptides to solution and crystal structure
    Sara Fuchs
    Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Ann N Y Acad Sci 998:93-100. 2003
  7. ncbi request reprint 3-D structure of serum paraoxonase 1 sheds light on its activity, stability, solubility and crystallizability
    Michal Harel
    Weizmann Institute of Science, Rehovot, Israel
    Arh Hig Rada Toksikol 58:347-53. 2007
  8. pmc Flexibility of aromatic residues in the active-site gorge of acetylcholinesterase: X-ray versus molecular dynamics
    Yechun Xu
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Biophys J 95:2500-11. 2008
  9. pmc In vitro detoxification of cyclosarin in human blood pre-incubated ex vivo with recombinant serum paraoxonases
    Yacov Ashani
    Department of Structural Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Toxicol Lett 206:24-8. 2011
  10. ncbi request reprint Three-dimensional structure determination of proteins related to human health in their functional context at The Israel Structural Proteomics Center (ISPC). This paper was presented at ICCBM10
    Shira Albeck
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Acta Crystallogr D Biol Crystallogr 61:1364-72. 2005

Collaborators

Detail Information

Publications54

  1. pmc An idea whose time has come
    Lucia Banci
    Genome Biol 8:408. 2007
  2. pmc Proteopedia - a scientific 'wiki' bridging the rift between three-dimensional structure and function of biomacromolecules
    Eran Hodis
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Genome Biol 9:R121. 2008
    ....
  3. ncbi request reprint FoldIndex: a simple tool to predict whether a given protein sequence is intrinsically unfolded
    Jaime Prilusky
    Biological Services, Weizmann Institute of Science, Rehovot 76100, Israel
    Bioinformatics 21:3435-8. 2005
    ..Sliding windows permit identification of large regions within a protein that possess folding propensities different from those of the whole protein...
  4. ncbi request reprint Complexes of alkylene-linked tacrine dimers with Torpedo californica acetylcholinesterase: Binding of Bis5-tacrine produces a dramatic rearrangement in the active-site gorge
    Edwin H Rydberg
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Med Chem 49:5491-500. 2006
    ....
  5. pmc The quaternary structure of amalgam, a Drosophila neuronal adhesion protein, explains its dual adhesion properties
    Tzviya Zeev-Ben-Mordehai
    Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    Biophys J 97:2316-26. 2009
    ....
  6. ncbi request reprint The binding site of acetylcholine receptor: from synthetic peptides to solution and crystal structure
    Sara Fuchs
    Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Ann N Y Acad Sci 998:93-100. 2003
    ..Our proposed model explains the strong antagonistic activity of alpha-BTX and accommodates much of the biochemical data on the mode of interaction of alpha-BTX with the AChR...
  7. ncbi request reprint 3-D structure of serum paraoxonase 1 sheds light on its activity, stability, solubility and crystallizability
    Michal Harel
    Weizmann Institute of Science, Rehovot, Israel
    Arh Hig Rada Toksikol 58:347-53. 2007
    ..The structure permits a detailed description of PON1's active site and suggests possible mechanisms for its catalytic activity on certain substrates...
  8. pmc Flexibility of aromatic residues in the active-site gorge of acetylcholinesterase: X-ray versus molecular dynamics
    Yechun Xu
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Biophys J 95:2500-11. 2008
    ..Thus, the protein can assume these conformations even in the absence of the ligand that permitted their experimental detection. These observations are pertinent to structure-based drug design...
  9. pmc In vitro detoxification of cyclosarin in human blood pre-incubated ex vivo with recombinant serum paraoxonases
    Yacov Ashani
    Department of Structural Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Toxicol Lett 206:24-8. 2011
    ..The results also permitted the refinement of a mathematical model for estimating the efficacious dose of rePON1s variants required for prophylaxis in humans...
  10. ncbi request reprint Three-dimensional structure determination of proteins related to human health in their functional context at The Israel Structural Proteomics Center (ISPC). This paper was presented at ICCBM10
    Shira Albeck
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Acta Crystallogr D Biol Crystallogr 61:1364-72. 2005
    ..This permits optimization of conditions at all stages of protein production and structure determination. A set of bioinformatics tools, which are implemented in our LIMS, is utilized to analyze each target...
  11. pmc Three-dimensional structure of a halotolerant algal carbonic anhydrase predicts halotolerance of a mammalian homolog
    Lakshmanane Premkumar
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Proc Natl Acad Sci U S A 102:7493-8. 2005
    ..A proposal for the functional significance of the halotolerance of CA XIV in the kidney is presented...
  12. ncbi request reprint Crystal structures of complexes of N-butyl- and N-nonyl-deoxynojirimycin bound to acid beta-glucosidase: insights into the mechanism of chemical chaperone action in Gaucher disease
    Boris Brumshtein
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 282:29052-8. 2007
    ..Together, these results have significance for understanding the mechanism of action of GlcCerase and the mode of GlcCerase chaperoning by imino sugars...
  13. pmc A server and database for dipole moments of proteins
    Clifford E Felder
    Department of Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel
    Nucleic Acids Res 35:W512-21. 2007
    ....
  14. ncbi request reprint Crystal packing mediates enantioselective ligand recognition at the peripheral site of acetylcholinesterase
    Haim Haviv
    Departments of Structural Biology and Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Am Chem Soc 127:11029-36. 2005
    ....
  15. pmc Characterization of gene-activated human acid-beta-glucosidase: crystal structure, glycan composition, and internalization into macrophages
    Boris Brumshtein
    Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
    Glycobiology 20:24-32. 2010
    ..These differences in glycosylation affect cellular internalization; the rate of velaglucerase alfa internalization into human macrophages is at least 2-fold greater than that of imiglucerase...
  16. pmc Acetylcholinesterase: from 3D structure to function
    Hay Dvir
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Chem Biol Interact 187:10-22. 2010
    ....
  17. ncbi request reprint The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design
    Harry M Greenblatt
    Departments of Structural Biology and Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Am Chem Soc 126:15405-11. 2004
    ..It is proposed that flexibility of this loop may permit the binding of inhibitors such as galanthamine, which are too bulky to penetrate the narrow neck of the gorge formed by Tyr121 and Phe330 as seen in the crystal structure...
  18. pmc The synaptic acetylcholinesterase tetramer assembles around a polyproline II helix
    Hay Dvir
    Dapartment of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    EMBO J 23:4394-405. 2004
    ..The P59Q mutation in ColQ, which causes congenital endplate AChE deficiency, and is located within the PRAD, disrupts crucial WAT-WAT and WAT-PRAD interactions. A model is proposed for the synaptic AChE(T) tetramer...
  19. ncbi request reprint Acetylcholinesterase: a multifaceted target for structure-based drug design of anticholinesterase agents for the treatment of Alzheimer's disease
    Harry M Greenblatt
    Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    J Mol Neurosci 20:369-83. 2003
    ..The noncovalent inhibitors vary greatly in their structures and bind to different sites of the enzyme, offering many different starting points for future drug design...
  20. pmc Induced-fit or preexisting equilibrium dynamics? Lessons from protein crystallography and MD simulations on acetylcholinesterase and implications for structure-based drug design
    Yechun Xu
    Department of Structural Biology, Weizmann Institute of Science, 76100 Rehovot, Israel
    Protein Sci 17:601-5. 2008
    ..Conformational changes upon ligand binding thus involve preexisting equilibrium dynamics. Consequently, rational drug design could benefit significantly from conformations monitored by MD simulations of native targets...
  21. pmc Biophysical characterization of the unstructured cytoplasmic domain of the human neuronal adhesion protein neuroligin 3
    Aviv Paz
    Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    Biophys J 95:1928-44. 2008
    ..However, several of these techniques indicate that it is not fully extended, but becomes significantly more extended under denaturing conditions...
  22. doi request reprint The crystal structure of a complex of acetylcholinesterase with a bis-(-)-nor-meptazinol derivative reveals disruption of the catalytic triad
    Aviv Paz
    Department of Structural Biology and Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Med Chem 52:2543-9. 2009
    ..These findings may facilitate rational design of new meptazinol-based acetylcholinesterase inhibitors...
  23. doi request reprint Amalgam, an axon guidance Drosophila adhesion protein belonging to the immunoglobulin superfamily: over-expression, purification and biophysical characterization
    Tzviya Zeev-Ben-Mordehai
    Department of Structural Biology, Weizmann Institute of Science, Rehovoth 76100, Israel
    Protein Expr Purif 63:147-57. 2009
    ..Furthermore, both purified fractions of amalgam were shown to interact with Torpedo californica acetylcholinesterase, a structural homolog of neurotactin...
  24. doi request reprint Directed evolution of serum paraoxonase PON3 by family shuffling and ancestor/consensus mutagenesis, and its biochemical characterization
    Olga Khersonsky
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Biochemistry 48:6644-54. 2009
    ..PON3 also exhibits potentially anti-atherogenic functions, although at levels lower than those of PON1...
  25. pmc Molecular basis of reduced glucosylceramidase activity in the most common Gaucher disease mutant, N370S
    Marc N Offman
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 285:42105-14. 2010
    ..Such analysis provides a new framework for determination of the structure of other Gaucher disease mutants and suggests new approaches for rational drug design...
  26. doi request reprint Cyclodextrin-mediated crystallization of acid β-glucosidase in complex with amphiphilic bicyclic nojirimycin analogues
    Boris Brumshtein
    Department of Structural Biology, Weizmann Institute of Science, Rehovot, 76100, Israel
    Org Biomol Chem 9:4160-7. 2011
    ..Our results further suggest that cyclodextrin derivatives might serve as suitable delivery systems of amphiphilic glycosidase inhibitors in a biomedical context...
  27. ncbi request reprint X-ray structure of human acid-beta-glucosidase covalently bound to conduritol-B-epoxide. Implications for Gaucher disease
    Lakshmanane Premkumar
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Biol Chem 280:23815-9. 2005
    ....
  28. ncbi request reprint Analysis of genetic polymorphisms in acetylcholinesterase as reflected in different populations
    Yehudit Hasin
    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel
    Curr Alzheimer Res 2:207-18. 2005
    ....
  29. ncbi request reprint Structural comparison of differently glycosylated forms of acid-beta-glucosidase, the defective enzyme in Gaucher disease
    Boris Brumshtein
    Department of Structural Biology, Weizmann Institute of Science, Israel
    Acta Crystallogr D Biol Crystallogr 62:1458-65. 2006
    ..Comparison of the structure of acid-beta-glucosidase with that of xylanase, a bacterial enzyme from a closely related protein family, demonstrates a close correspondence between the active-site residues of the two enzymes...
  30. doi request reprint Acid beta-glucosidase: insights from structural analysis and relevance to Gaucher disease therapy
    Yaacov Kacher
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Biol Chem 389:1361-9. 2008
    ..We also discuss the stability of Cerezyme, which can be altered by modification of its N-glycan chains with possible implications for improved ERT in Gaucher disease...
  31. doi request reprint Crystal structure of thioflavin T bound to the peripheral site of Torpedo californica acetylcholinesterase reveals how thioflavin T acts as a sensitive fluorescent reporter of ligand binding to the acylation site
    Michal Harel
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Am Chem Soc 130:7856-61. 2008
    ..This rotation may allow some relaxation of the strict coplanarity of the aromatic rings in the bound thioflavin T and result in partial quenching of its fluorescence...
  32. doi request reprint Assessment of CASP8 structure predictions for template free targets
    Moshe Ben-David
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Proteins 77:50-65. 2009
    ....
  33. ncbi request reprint The 3D structure of the anticancer prodrug CPT-11 with Torpedo californica acetylcholinesterase rationalizes its inhibitory action on AChE and its hydrolysis by butyrylcholinesterase and carboxylesterase
    Michal Harel
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Chem Biol Interact 157:153-7. 2005
    ..Modeling of the complexes of CPT-11 with mammalian butyrylcholinesterase and carboxylesterase, both of which are known to hydrolyze the drug, shows how binding to either of the two enzymes yields a productive substrate-enzyme complex...
  34. pmc Structure of estradiol metal chelate and estrogen receptor complex: the basis for designing a new class of selective estrogen receptor modulators
    Min Jun Li
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Med Chem 54:3575-80. 2011
    ..6 Å resolution. This structure provides important information pertinent to the design of novel functional ERα targeted probes for clinical applications...
  35. ncbi request reprint Natural protein engineering: a uniquely salt-tolerant, but not halophilic, alpha-type carbonic anhydrase from algae proliferating in low- to hyper-saline environments
    Umesh K Bageshwar
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
    Protein Eng Des Sel 17:191-200. 2004
    ..Its unique features make dCA I a useful model to understand the physico-chemical basis of halotolerance and protein-salt interactions in general...
  36. doi request reprint Proteopedia: a status report on the collaborative, 3D web-encyclopedia of proteins and other biomolecules
    Jaime Prilusky
    Bioinformatics Unit, Biological Services Unit, Weizmann Institute of Science, Rehovot 76100, Israel
    J Struct Biol 175:244-52. 2011
    ..We also describe Proteopedia's use for 3D visualization in structure-related pedagogy...
  37. doi request reprint Assessment of disorder predictions in CASP8
    Orly Noivirt-Brik
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    Proteins 77:210-6. 2009
    ....
  38. doi request reprint High throughput pH optimization of protein crystallization
    Ran Meged
    Israel Structural Proteomics Center ISPC, Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    Methods Mol Biol 426:411-8. 2008
    ..This chapter describes a protocol for such automated systems, which permits easy construction of pH optimization grids using any desired fixed buffer set with varying ionic strengths directly dispensed into the crystallization plate...
  39. ncbi request reprint Acetylcholinesterase: 'classical' and 'non-classical' functions and pharmacology
    Israel Silman
    Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
    Curr Opin Pharmacol 5:293-302. 2005
    ..Both of these actions involve the so-called 'peripheral' anionic site at the entrance to the active-site gorge. Novel anticholinesterases are targeted against this site, rather than against the active site at the bottom of the gorge...
  40. ncbi request reprint Operational definition of intrinsically unstructured protein sequences based on susceptibility to the 20S proteasome
    Peter Tsvetkov
    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel
    Proteins 70:1357-66. 2008
    ..Taken together, our results thus suggest that the 20S proteasome degradation assay provides a powerful system for operational definition of IUPs...
  41. pmc X-ray structure of human acid-beta-glucosidase, the defective enzyme in Gaucher disease
    Hay Dvir
    1 Departments of Structural Biology and Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel
    EMBO Rep 4:704-9. 2003
    ..The structure provides the possibility of engineering improved GlcCerase for enzyme-replacement therapy, and for designing structure-based drugs aimed at restoring the activity of defective GlcCerase...
  42. doi request reprint Directed evolution of hydrolases for prevention of G-type nerve agent intoxication
    Rinkoo D Gupta
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel
    Nat Chem Biol 7:120-5. 2011
    ..We then demonstrated the in vivo prophylactic activity of an evolved variant. These evolved variants and the newly developed screens provide the basis for engineering PON1 for prophylaxis against other G-type agents...
  43. ncbi request reprint A paradigm for single nucleotide polymorphism analysis: the case of the acetylcholinesterase gene
    Yehudit Hasin
    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Hum Mutat 24:408-16. 2004
    ....
  44. ncbi request reprint Design and synthesis of peptides that bind alpha-bungarotoxin with high affinity and mimic the three-dimensional structure of the binding-site of acetylcholine receptor
    Ephraim Katchalski-Katzir
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Biophys Chem 100:293-305. 2003
    ..The procedure described in this article may serve as a paradigm for obtaining high-affinity peptides in biochemical systems that contain a ligand and a receptor molecule...
  45. ncbi request reprint Acetylcholinesterase complexed with bivalent ligands related to huperzine a: experimental evidence for species-dependent protein-ligand complementarity
    Dawn M Wong
    Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel
    J Am Chem Soc 125:363-73. 2003
    ..The results offer new insights into factors affecting protein-ligand complementarity within the gorge and should assist the further development of improved AChE inhibitors...
  46. ncbi request reprint The intracellular domain of the Drosophila cholinesterase-like neural adhesion protein, gliotactin, is natively unfolded
    Tzviya Zeev-Ben-Mordehai
    Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
    Proteins 53:758-67. 2003
    ..In addition, Gli-cyt was shown to possess charge and hydrophobic properties characteristic of natively unfolded proteins (i.e., proteins that, when purified, are intrinsically disordered under physiologic conditions in vitro)...
  47. ncbi request reprint New directions in the treatment of Gaucher disease
    Anthony H Futerman
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Trends Pharmacol Sci 25:147-51. 2004
  48. doi request reprint Acetylcholinesterase: how is structure related to function?
    Israel Silman
    Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel
    Chem Biol Interact 175:3-10. 2008
    ....
  49. ncbi request reprint eMovie: a storyboard-based tool for making molecular movies
    Eran Hodis
    Department of Structural Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
    Trends Biochem Sci 32:199-204. 2007
    ..This tool is a plug-in for the open-source molecular graphics program PyMOL, and enables experts and novices alike to produce informative and high-quality molecular animations...
  50. ncbi request reprint HalX: an open-source LIMS (Laboratory Information Management System) for small- to large-scale laboratories
    Jaime Prilusky
    Israel Structural Proteomics Center, Weizmann Institute of Science, Rehovot 76100, Israel
    Acta Crystallogr D Biol Crystallogr 61:671-8. 2005
    ..This should lead to much improved management and tracking of structural genomics experimental data...
  51. ncbi request reprint Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes
    Michal Harel
    Department of Structural Biology, The Weizmann Institute of Science, Rehovot 76 100, Israel
    Nat Struct Mol Biol 11:412-9. 2004
    ....
  52. ncbi request reprint Proteomic signatures: amino acid and oligopeptide compositions differentiate among phyla
    Itsik Pe'er
    Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel
    Proteins 54:20-40. 2004
    ..Finally, we report that species composition signatures preserve evolutionary memory, providing a new method to compare phylogenetic relationships among species that avoids problems of sequence alignment and ortholog detection...
  53. ncbi request reprint Identification, cDNA cloning, expression, crystallization and preliminary X-ray analysis of an exceptionally halotolerant carbonic anhydrase from Dunaliella salina
    Lakshmanane Premkumar
    Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
    Acta Crystallogr D Biol Crystallogr 59:1084-6. 2003
    ..The asymmetric unit contains two molecules of the protein, which corresponds to V(M) = 2.65 A(3) Da(-1) and a solvent content of 52.7%...
  54. ncbi request reprint Structure of a complex of the potent and specific inhibitor BW284C51 with Torpedo californica acetylcholinesterase
    Clifford E Felder
    Department of Structural Biology, Weizmann Institute, Rehovot, Israel
    Acta Crystallogr D Biol Crystallogr 58:1765-71. 2002
    ..The relative strength of binding of bisquaternary inhibitors to acetylcholinesterase and the effect of several mutations of the enzyme are discussed in the context of the respective X-ray structures of their complexes with the enzyme...