User:Boris Brumshtein

CVCV

Personal InformationPersonal Information

Name: Boris Brumshtein

Languages: English, Hebrew and Russian

Current residence: Rehovot, Israel.

Contact InformationContact Information

Department of Structural Biology, Weizmann Institute of Science Rehovot, 76100, Israel

E-mail: Boris.Brumshtein@weizmann.ac.il

Tell: +972-52-6902631 (private) +972-8-9342647 (work)

EducationEducation

2003 - present Direct PhD program at the Weizmann Institute of Science, Faculty of Chemistry, Department of Structural Biology. Estimated graduation - summer 2008. Scientific advisors: Prof. Joel L. Sussman, Prof. Israel Silman, Prof. Anthony H. Futerman Thesis topic: "Structural and biochemical studies on acid-beta-glucosidase, the defected protein in Gaucher disease".

2002-2003 MSc student, Weizmann Institute of Science, Faculty of Chemistry, Department of Structural Biology. Scientific advisor: Prof. Joel Sussman.

1999-2002 BA in Biochemistry, Technion, Israel Institute of Science and Technology, Faculty of Chemistry, cum laude.

QualificationsQualifications

In my research I employ different protein biochemistry, enzymology and crystallography methods, thus I gained a lot of experience in the following techniques:

CrystallographyCrystallography

- Protein crystallization utilizing microbatch crystallization, IMPAX I-5, Oryx and Mosquito crystallization robots.

- Ab initio crystallization and crystals optimization. Various crystallization techniques, such as: soaking, co-crystallization, crystallization in presence of heavy metals for phasing, etc.

- Crystal handling and manipulations, micro-manipulations with ZEISS microscope/manipulator system.

- Data acquisition using Rigaku Raxis 4/4++ or synchrotron x-ray sources.

- X-ray data processing software: XDS, HKL2000.

- Protein structure determination using MR, SIR, MIR, MAD, SIRAS approaches with CNS, SHELX and CCP4 software suits.

- Molecular modeling, visualization and analysis software: PyMol, Coot, XtalView, O, CCP4, APBS.

- Docking and small molecule/drug database mining with AutoDock - drug docking and virtual screening, Cambridge Structure Database (CSB), ZINC, ChemOffice.

Molecular biology and biochemistryMolecular biology and biochemistry

- Protein cloning and expression in E.Coli.

- Biochemical and protein purification techniques: HPLC, FPLC, Ni-columns, Ion exchange columns, acryl-amide gels, size exclusion, affinity chromatography, gradient and analytical ultracentrifugation, ultra-filtration, Mini Prep cell, etc.

- Drug-Protein interaction analysis employing various structural, biochemical and biophysical assays such as: enzymatic assays, ELIZA, circular dichroism, dynamic light scattering, mass-spec, BiaCore, analytical ultracentrifugation, etc.

Programming languagesProgramming languages

-Unix, C, Perl, Matlab, Java (basic programming).

LIST OF PUBLICATIONSLIST OF PUBLICATIONS

1. Brumshtein B, Greenblatt HM, Butters TD, Shaaltiel Y, Aviezer D, Silman I, Futerman AH, Sussman JL. 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. J.Biol. Chem., Vol. 282, Issue 39, 29052-29058, (2007).
2. Brumshtein, B., Wormald, M. R., Silman, I., Futerman, A. H. & Sussman, J. L. Structural comparison of differently glycosylated forms of acid-beta-glucosidase, the defective enzyme in Gaucher disease. Acta Crystallogr D Biol Crystallogr 62, 1458-65 (2006).
3. Rydberg EH, Brumshtein B, Greenblatt HM, Wong DM, Shaya D, Williams LD, Carlier PR, Pang YP, Silman I, Sussman JL. Complexes of alkylene-linked tacrine dimers with Torpedo californica acetylcholinesterase: Binding of Bis5- tacrine produces a dramatic rearrangement in the active-site gorge. J Med Chem 49, 5491-500 (2006).
4. Harel M, Hyatt JL, Brumshtein B, Morton CL, Wadkins RM, Silman I, Sussman JL, Potter PM. 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. Chem Biol Interact 157-158, 153-7 (2005).
5. Hyatt JL, Tsurkan L, Morton CL, Yoon KJ, Harel M, Brumshtein B, Silman I, Sussman JL, Wadkins RM, Potter PM. Inhibition of acetylcholinesterase by the anticancer prodrug CPT-11. Chem Biol Interact 157-158, 247-52 (2005).
6. Harel M, Hyatt JL, Brumshtein B, Morton CL, Yoon KJ, Wadkins RM, Silman I, Sussman JL, Potter PM. The crystal structure of the complex of the anticancer prodrug 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin (CPT- 11) with Torpedo californica acetylcholinesterase provides a molecular explanation for its cholinergic action. Mol Pharmacol 67, 1874-81 (2005).
7. Harel M, Aharoni A, Gaidukov L, Brumshtein B, Khersonsky O, Meged R, Dvir H, Ravelli RB, McCarthy A, Toker L, Silman I, Sussman JL, Tawfik DS. Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 11, 412-9 (2004).
8. Adir, N., Rukhman, V., Brumshtein, B. & Anati, R. Preliminary X-ray crystallographic analysis of a soluble form of MntC, a periplasmic manganese- binding component of an ABC-type Mn transporter from Synechocystis sp. PCC 6803. Acta Crystallogr D Biol Crystallogr 58, 1476-8 (2002). PMID:12198307

PROTEIN DATABANK DEPOSITIONSPROTEIN DATABANK DEPOSITIONS

1. 1odc STRUCTURE OF ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH N-4'-QUINOLYL-N'-9"-(1",2",3",4"- TETRAHYDROACRIDINYL)-1,8-DIAMINOOCTANE AT 2.2A RESOLUTION
2. 1u65 Ache W. CPT-11
3. 1ut6 STRUCTURE OF ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH N-9-(1',2',3',4'-TETRAHYDROACRIDINYL)-1,8-DIAMINOOCTANE AT 2.4 ANGSTROMS RESOLUTION
4. 1v04 SERUM PARAOXONASE BY DIRECTED EVOLUTION
5. 2ckm TORPEDO CALIFORNICA ACETYLCHOLINESTERASE COMPLEXED WITH ALKYLENE-LINKED BIS-TACRINE DIMER (7 CARBON LINKER)
6. 2cmf TORPEDO CALIFORNICA ACETYLCHOLINESTERASE COMPLEXED WITH ALKYLENE-LINKED BIS-TACRINE DIMER (5 CARBON LINKER)
7. 2j25 PARTIALLY DEGLYCOSYLATED GLUCOCERAMIDASE
8. 2v3d ACID-BETA-GLUCOSIDASE WITH N-BUTYL-DEOXYNOJIRIMYCIN
9. 2v3e ACID-BETA-GLUCOSIDASE WITH N-NONYL-DEOXYNOJIRIMYCIN

The page is always under construction ; last update Boris Brumshtein 14:12, 8 June 2008 (IDT)

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