Steve Pascal

Associate Professor in Physics/ Director of BioNMR Research (Centre for Structural Biology)

Email	S.Pascal@massey.ac.nz
Phone	+64 6 (06) 356-9099 Ext 3558
Fax	+64 6 350-5682
Location	Science Tower C5.02 Turitea Site Palmerston North Campus Private Bag 11222 Palmerston North 4442 New Zealand

Director of BioNMR Research. Contact Steve for queries about NMR.

New book to demystify NMR - Massey News Sep 29, 2008

Qualifications and Achievement

BS Nebraska Wesleyan (1985); MA Kent State (1987); PhD Florida State (1993); MRC postdoctoral fellow, University of Toronto and Hospital for Sick Children (1993-1996); Assistant Professor of Biochemistry and Biophysics, University of Rochester Medical Center (1996-2003).

Commenced current position in July, 2003. IFS Distinguished Teaching Award (2006). Promoted to Associate Professor for 2010.

Teaching

124.101 Physics I(a) internally in Semester 1
124.111 Physics for Life Sciences internally in Semester 1
124.226 Quantum and Statistical Physics internally in Semester 2
124.230 Biophysics internally in Semester 2
124.316 Advanced Experimental Physics internally in Semester 2
124.325 Advanced Quantum Physics internally in Semester 1

Research Interests

My research cluster(s):

NMR of Large Biomolecules and Complexes

Recent NMR advances (e.g. deuteration and quadruple-resonance, TROSY, cryogenic probes, Residual Dipolar Couplings) allow extension of structure determination to complexes or multi-domain proteins in the 100-kDa range. Once individual domain structures are determined via more established X-ray or NMR methods, these more advanced technologies can be combined with computational approaches to bring the domains or molecules into their proper relative alignment. Given the wealth of domain structure information becoming available through structural proteomics projects together with advances in bioinformatics and modeling, the NMR-based approach to large molecules and complexes shows great promise in addressing the next major initiative in genome-based research: deciphering the network of inter-molecular and inter-domain interactions.

Residual Dipolar Coupling improves NMR structure determination

Molecules which normally reorient isotropically in solution can be prompted to become weakly anisotropic via immersion in a liquid crystalline solution. This anisotropy allows measurement of the direct coupling between two nuclear dipoles, which otherwise would time-average to zero. As this coupling contains an angular dependence, its survival (residual dipolar coupling or RDC) allows the extraction of angular information. Hence it is now possible to determine the angle between, e.g., two H-N bond vectors from extreme ends of a large molecule, or between bond vectors from two different molecules in a complex. This can dramatically increase the capabilities of NMR to accurately and precisely determine the structure of proteins and nucleic acids.

Computer-aided understanding of NMR experiments

We have developed a method whereby the magnetization transfer pathway during simple and complicated NMR experiments can be visualized. The approach involves colour-coded vector animations and will shortly be available with an accompanying text.

NMR Book NOW available: order online

NMR Primer: an HSQC-based approach (with vector animations). S.M. Pascal. Animations by Jennie M. McKelvie. IM Publications, 2008.

Recent Grants

Marsden (2009) of $735,000 over 3 years for the project Looking over a four-leaf clover: structural characterisation of a critical picornaviral RNA clover leaf and its interaction with a viral fusion protein (in collaboration with Prof. Jill Trewhella, U. Sydney/U. Utah;Dr. Kaushik Dutta, NYSBC)
RSNZ-Marsden Grant (2006) of $720000 over 3 years for the project The Zipper, the Butterfly and Death: Structural studies of an apoptosis-triggering protein-protein interaction linked to prostate cancer and neurodegenerative disease (in collaboration with Dr. Kaushik Dutta, NYSBC; Prof. Vivek Rangnekar, U. Kentucky)
Fund for Innovation and Excellence in Teaching Award (2006) of $16300 over 1 years for the project Interactive visualization of NMR spectroscopy (in collaboration with Pat Edwards and Jennie McKelvie)
Health Research Council Grant (2006) of $28000 over 1 years for the project Purchase of an automated tune and match (ATM) module for 700 MHz NMR Cryoprobe (in collaboration with Geoff Jameson and Pat Edwards)
RSNZ-Marsden Grant (2004) of $630000 over 3 years for the project Picornaviral Replication: Structures and Interactions of Two Key Viral Molecules
Hort Research Grant (2003) of $83115 over 6 years for the project Biomedial Applications of Proteins from Plant Genes (in collaboration with Dr. Peter Farley, IMBS)

Graduate Students or Postdoctoral Fellows

Martin Schwalbe for PhD
Hari Venugopal for PhD

Former Graduate Students

Jo Claridge to January, 2010
Sachin Kate to January, 2010

2008 group photo

Recent Publications

Sun, X., Jones, W.T., Harvey, D., Edwards, P.J.B., Pascal, S.M., Kirk, C., Considine, T., Sheerin, D.J., Rakonjac, J., Oldfield, C.J., Xue, B., Dunker, A.K., Uversky, V.N. (2010) N-terminal domains of Della proteins are intrinsically unstructured in the absence of interaction with GID1 GA receptors. J. Biol. Chemistry 285 15 11557-11571
Edwards, P.J.B, Kakubayashi, M., Dykstra, R., Pascal, S.M., Williams, M.A.K. (2010) Rheo-NMR Studies of an Enzymatic Reaction: Evidence of a Shear-Stable Macromolecular System. Biophysical J. 98 9 1986-1994
Headey SJ, MacAskill UK, Wright MA, Claridge JK, Edwards PJB, Farley PC, Christeller JT, Laing WA, Pascal SM (2010) Solution Structure of the Squash Aspartic Acid Proteinase Inhibitor (SQAPI) and Mutational Analysis of Pepsin Inhibition J. Biol. Chemistry 285 27019-27025
Ponniah,K, Loo,TS, Edwards,PJ, Pascal,SM, Jameson,GB,Norris,GE (2010) The production of soluble and correctly folded recombinant bovine β-lactoglobulin variants A and B in Escherichia coli for NMR studies Protein Expression and Purification 70 2 283-289
Schwalbe M, Dutta K, Libich DS, Venugopal H, Claridge JK, Gell DA, Mackay JP, Edwards PJB, Pascal SM (2010) Two-state Conformational Equilibrium in the Par-4 Leucine Zipper Domain PROTEINS: Structure, Function and Bioinformatics 78 11 2433-2449

Selected Publications

Claridge JK, Headey SJ, Chow JYH, Schwalbe M, Edwards PJ, Jeffries CM, Venugopal H, Trewhella J, Pascal SM (2009) A picornaviral loop-to-loop replication complex Journal of Structural Biology 166 251-262
Libich�DS,�Schwalbe�M,�Venugopal�H,�Claridge�JK,�Edwards�PJ,�Dutta�K,�Pascal�SM� (2009) Intrinsic disorder and coiled-coil formation in prostate apoptosis response factor 4 The FEBS Journal 276 14 3710-3728
Dutta K, Cox CJ, Basavappa R, Pascal SM (2008) ¹⁵N relaxation studies of apo- M ts 1 : A dynamic S100 protein Biochemistry 47 29 7637-7647
Pascal�SM (2008) NMR primer: An HSQC-based approach IM Publications Chichester, UK 143 pp
Headey�SJ,�Huang�H, Claridge JK, Soares GA, Dutta�K,�Schwalbe�M,�Yang�D,�Pascal�SM� (2007) NMR structure of stem-loop D from human rhinovirus-14 RNA 13 3 351-360
Mukherjee�M,�Dutta�K,�Pascal�SM,�Fox�RO (2004) Backbone and side chain resonance assignments of domain III of the tick-borne Langat flavivirus envelope protein Journal of Biomolecular Nuclear Magnetic Resonance 29 535-536
Wu�J,�Fan�J,�Pascal�SM,�Yang�D (2004) General method for suppression of diagonal peaks in heteronuclear-edited NOESY spectroscopy Journal of the American Chemical Society 126 15018-15019
Dutta�K,�Engler�FA,�Cotton�L,�Alexandrov�A,�Bedi�GS,�Colquhoun�J,�Pascal SM (2003) Stabilization of a pH-sensitive apoptosis-linked coiled coil through single point mutations Protein Science 12 257-265
Dutta�K,�Cox�C,�Alexandrov�A,�Huang�H,�Basavappa�R,�Pascal�SM (2002) Sequence-specific chemical shift assignment and chemical shift indexing of murine apo-Mts1 Journal of Biomolecular Nuclear Magnetic Resonance 22 181-182
Cox�C,�Dutta�K,�Petri�E,�Hwang�W,�Lin�YH,�Pascal SM, Basavappa�R (2002) The regions of securin and cyclin B proteins recognized by the ubiquitination machinery are natively unfolded Federation of European Biochemical Society Letters 527 303-308
Dutta�K,�Cox�C,�Huang�H,�Basavappa R, Pascal SM (2002) Calcium coordination studies of the metastatic Mts1 protein Biochemistry 41 13 4239-4245
Cox�C,�Dutta K, Basavappa�R,�Zain SB, Pascal SM (2002) Sequence-specific chemical shift assignment of calcium-loaded murine S100A4 Journal of Biomolecular Nuclear Magnetic Resonance 23 2 153-154
Huang�H,�Alexandrov�A,�Chen�X,�Barnes�TW,�Zhang�H,�Dutta�K,�Pascal�SM (2001) Structure of an RNA hairpin from HRV-14 Biochemistry 40 8055-8064
Alexandrov A, Dutta K, Pascal�SM (2001) MBP fusion protein with a viral protease cleavage site: One-step cleavage/purification of insoluble proteins BioTechniques 30 6 2-5
Dutta�K,�Alexandrov�A,�Huang�H,�Pascal SM (2001) pH-induced folding of an apoptotic coiled coil Protein Science 10 2531-2540

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