Professor Michael W Parker, Associate Director of St. Vincent's Institute of Medical Research and Professorial Fellow and Professor at Melbourne University.
Brief CV:
Michael Parker has an extensive background in protein crystallography,
having worked in the field for more than 20 years and has been
involved in the structure determination of more than 30 proteins.
He runs a very productive protein crystallography laboratory with
over a dozen publications per year, mostly in high impact journals,
and numerous invitations to speak at national and international meetings.
His work at St. Vincent's has been supported by three prestigious fellowships: a Wellcome Trust Australian Senior Research Fellowship (1991 - 1995), an ARC Senior Research Fellowship (1997 - 2001) and an NHMRC Senior Principal Research Fellowship (2002-). His work in the field has been recognised by the award of the Selwyn-Smith Medical Research Prize (1994) by the University of Melbourne for the most outstanding research in a medical area over a 3 year period, the Boehringer-Mannheim Medal (1996) for best young Australian biochemist awarded by the Australian Society for Biochemistry and Molecular Biology, the Gottschalk Medal (1999) of the Australian Academy of Science for distinguished research in the medical and biological sciences and the Walter Burfitt Prize (2002) of the Royal Society of New South Wales for the highest levels of scientific achievement in Australia or New Zealand over the last 6 years.
He has published 142 papers and 5 patents including 109 in peer-reviewed journals including 4 Nature, 3 Nature Struct. Biol., 3 Cell, 2 Proc. Natl. Acad. Sci, 4 Trends Biochem Soc. and 4 EMBO J. papers. Ten of his papers have been cited more than 100 times in the literature. Five have had prominent News & Views coverage in journals such as Science, Nature, Nature Struct. Biol. Three have been highlighted with journal covers in Blood, J. Mol. Biol. and Biochem. J.
His standing in the scientific community has also been recognised by invitations to join the Editorial Advisory Board of Protein Science (1998-), Member and Chair of the Executive Committee of the Australian Synchrotron Research Program (1998-), Chair of the BioCARS (Protein crystallography) Sub-Committee of the ASRP (1998-), a member of the Scientific Advisory Board of Biota Holdings Ltd (1994-2000), Victorian representative member of Council for the Australian Society for Biochemistry and Molecular Biology (1999-2001), Member of a NHMRC Discipline Panel (1999-2001), member of the Victorian Government Biotechnology Focus Group and Scientific advisor/organiser of 3 international meetings. Michael is an Associate Director of St. Vincent's Institute of Medical Research (1999-) and a Professorial Fellow at Melbourne University.
Brief summary of expertise and significant research achievements:
Michael is regarded as one of the world leaders in the study of
glutathione transferases. He has worked in the field for over 12 years
and has published 65 papers in the area including an invited review.
Many of the publications have been published in high impact journals
such as EMBO J., J. Biol. Chem., J. Mol. Biol. and Structure. Three of
the papers have been cited more than 100 times:
Biochim. Biophys. Acta, 1205, 1-18 (210 citations),
EMBO J., 14, 2133-2143 (171 citations) and J. Mol. Biol. 227, 214-226
(205 citations). The CI is a regularly invited speaker at international
meetings on detoxifying enzymes (International ISSX-Workshop on
Glutathione S-Transferases, The Netherlands, April, 1995; International
Workshop on Glutathione Transferases, Rome, Italy, November, 1997;
British Toxicology Society Annual Meeting, Keele, UK, April, 1999;
Symposium on Biocrystallography for Medicine and Biotechnology, Rome,
Italy, December, 1999; International Conference on Glutathione
Transferases, Uppsala, Sweden, May, 2000; Symposium on Xenobiotic
Enzymology, Pacifichem 2000, Honolulu, Hawaii, December 2000).
He was Chair of the Structure and Folding session at the Swedish meeting.
Michael Parker is also regarded as a leading figure in the study of membrane-associating proteins with 49 papers in the field including 6 invited reviews, a book and 2 patents. The impact of his work has also been demonstrated by invited oral presentations at membrane protein sessions of 10 prestigious international meetings since 1989. He has been involved in the structure determination of a number of membrane-associating proteins (colicins, phosphoporin, aerolysin, perfringolysin O, hemolysin, APP, cytokine receptor) and hence has extensive experience in applying structural biology tools to the study of these proteins.
International linkages:
Italy, Sweden, US, Canada, United Kingdom
Students and postdocs likely to be involved in or use the Network:
Students:
Lorien Parker
Research Assistants:
Hooi Ling Ng
Postdocs/Research Fellows:
Galina Polekhina
Julian Adams
Susanne Feil
Luke Miles
Website:
http://www.svimr.unimelb.edu.au/parker.htm
Relevant grants:
| 2004-2005 | Structural studies of glutathione transferases: a model system for functional genomics and drug design, $220,000. |
| 2004-2005 | MW Parker, Structural studies of amyloid precursor protein, NHMRC, Project, $316,000. |
| 2004-2005 | MW Parker, BA Cromer, Structural studies of the GABA receptor, NHMRC, project, $320,000. |
| 2004-2005 | D Bowtell, MW Parker, C House, G Polekhina, Structural determinants of Siah ubiquitin ligase complexes, NHMRC, project, $170,000. |
| 2004-2005 | MW Parker, Structural studies of bacterial pore-forming toxins, NHMRC, project MW Parker, Structural studies of bacterial pore-forming toxins, NHMRC, project, $170,000. |
Relevant publications (past 5 years):
73. Rossjohn, J., Cappai, R., Feil, S.C., Henry, A.,
McKinstry, W.J., Galatis, D., Hesse, L., Multhaup, G., Beyreuther,
K., Masters, C.L. & Parker, M.W. (1999) Crystal structure of the
N-terminal, growth factor-like domain of Alzheimer's amyloid
precursor protein. Nature Struct. Biol., 6, 327-331.
74. Allocati, N., Casalone, E., Masulli, M., Ceccarelli, I.,
Carletti, E., Parker, M.W. & Di Ilio, C. (1999) Functional analysis
of the evolutionary conserved proline 53 residue in Proteus
mirabilis glutathione transferase B1-1. FEBS Lett., 445, 347-350.
75. Polekhina, G., Board, P.G., Gali, R.R., Rossjohn, J. &
Parker, M.W. (1999) Molecular basis of glutathione synthetase
deficiency and a rare gene permutation event. EMBO J., 18, 3204-3213.
76. Shatursky, O., Heuck, A.P., Shepard, L.A., Rossjohn, J.,
Parker, M.W., Johnson, A.E. & Tweten, R.K. (1999) The mechanism of
membrane insertion for a cholesterol-dependent cytolysin: a novel
paradigm for pore-forming toxins. Cell, 99, 293-299.
77. Oakley, A.J., Lo Bello, M., Nuccetelli, M., Mazzetti, A.P. &
Parker, M.W. (1999) The ligandin (non-substrate) binding site of human
pi class glutathione transferase is located in the electrophile
binding site (H-site). J. Mol. Biol., 291, 913-926.
78. Gilbert, R.J.C., Heenan, R.K., Timmins, P.A., Gingles, N.A.,
Mitchell, T.J., Rowe, A.J., Rossjohn, J., Parker, M.W. Andrew, P.W. &
Byron, O. (1999) Studies of the structure and mechanism of a bacterial
protein toxin by analytical ultracentrifugation and small-angle
neutron scattering. J. Mol. Biol., 293, 1145-1160.
79. Gilbert, R.J.C., Jiménez, J.L., Chen, S., Tickle, I., Rossjohn, J.,
Parker, M.W., Andrew, P.W. & Saibil, H. (1999) Two structural transitions
in membrane pore formation by pneumolysin, the pore-forming toxin of
Streptococcus pneumoniae. Cell, 97, 647-655.
80. Flanagan, J.U., Rossjohn, J., Parker, M.W., Board, P.G. &
Chelvanayagam, G. (1999) Mutagenic analysis of conserved arginine residues
in and around the novel sulfate binding pocket of the human theta class
glutathione transferase T2-2. Protein Sci., 8, 2205-2212.
81. Caccuri, A.M., Antonini, G., Board, P.G., Parker, M.W., Nicotra, M.,
Lo Bello, M., Federici, G. & Ricci, G. (1999) Proton release upon binding
of glutathione to alpha, mu and delta class glutathione transferases.
Biochem. J., 344, 419-425.
82. Dunstone, M.A., Dai, W., Whisstock, J.C., Rossjohn, J., Pike, R.N.,
Feil, S.C., Bonniec, B.F., Parker, M.W. & Bottomley, S.P. (2000) Cleaved
antitrypsin polymers at atomic resolution. Protein Sci., 9, 417-420.
83. Rossjohn, J., McKinstry, W.J., Woodcock, J.M., McClure, B.J.,
Hercus, T.R., Parker, M.W., Lopez, A.F. & Bagley, C.J. (2000) Structure of
the activation domain of the GM-CSF/IL-3/IL-5 receptor common b chain
bound to an antagonist. Blood, 95, 2491-2498. (This paper was designated
the plenary paper of the issue and a picture of the structure appeared on
the front cover of the journal).
84. Flanagan, J.U., King, W., Parker, M.W., Board, P.G. &
Chelvanayagam, G. (2000) Ab initio calculations on hidden modulators of
theta class glutathione transferase activity. Proteins Struct. Funct.
Genetics, 39, 235-243.
85. Njålsson, R., Carlsson, K., Olin, B., Carlsson, B., Whitbread,
L., Polekhina, G., Parker, M.W., Norgren, S., Mannervik, B., Board, P.G. &
Larsson, A. (2000) Kinetic properties of missense mutations in patients
with glutathione synthetase deficiency. Biochem. J., 349, 275-279.
86. Rossjohn, J., McKinstry, W.J., Oakley, A.J., Parker, M.W.,
Stenberg, G., Mannervik, B., Dragani, B., Cocco, R. & Aceto, A.
(2000) Structures of thermolabile mutants of human glutathione
transferase P1-1. J. Mol. Biol., 302, 295-302.
87. * Micaloni, C., Mazzetti, A.P., Nuccetelli, M., Rossjohn, J.,
McKinstry, W.J., Antonini, G., Caccuri, A.M., Oakley, A.J., Federici,
G., Ricci, G., Parker, M.W. & Lo Bello, M. (2000) Valine 10 may act as a
driver for product release from the active site of human glutathione
transferase P1-1. Biochemistry, 39, 15961-15970.
88. Allocati, N., Casalone, E., Masulli, M., Polekhina, G.,
Rossjohn, J., Parker, M.W. & Di Ilio, C. (2000) Evaluation of the role
that two conserved active-site residues in Beta class glutathione
transferases. Biochem. J., 351, 341-346.
89. Caccuri, A.M., Antonini, G., Board, P.G., Flanagan,
J., Parker, M.W., Paolesse, R., Turella, P., Federici, G., Lo Bello, M. &
Ricci, G. (2001) Human glutathione transferase T2-2 discloses some
evolutionary strategies for optimization of substrate binding to the
active site of glutathione transferases. J. Biol. Chem., 276, 5427-5431.
90. Caccuri, A.M., Antonini, G., Board, P.G., Flanagan, J.,
Parker, M.W., Paolesse, R., Turella, P., Chelvanayagam, G. & Ricci, G.
(2001) Human glutathione transferase T2-2 discloses some evolutionary
strategies for optimization of the catalytic activity of glutathione
transferases. J. Biol. Chem., 276, 5432-5437.
91. Polekhina, G., Board, P.G., Blackburn, A.C. & Parker, M.W.
(2001) The crystal structure of maleylacetoacetate isomerase/glutathione
transferase zeta reveals the molecular basis for its remarkable
catalytic promiscuity. Biochemistry, 40, 1567-1576.
92. Hotze, E.M., Wilson-Kubalek, E.M., Rossjohn, J., Parker, M.W.,
Johnson, A.E. & Tweten, R.K. (2001) Arresting pore formation of a
cholesterol-dependent cytolysin by disulfide trapping synchronizes the
insertion of the transmembrane b-sheet from a prepore intermediate.
J. Biol. Chem., 276, 8261-8268.
93. Blackburn, A.C., Coggan, M., Tzeng, H-F., Lantum, H., Polekhina,
G., Parker, M.W., Anders, M.W. & Board, P.G. (2001) GSTZ1d, a new allele
of glutathione transferase Zeta and maleylacetoacetate isomerase.
Pharmacogenetics, 11, 671-678.
94. Gisi, D., Maillard, J., Flanagan, J.U., Rossjohn, J.,
Chelvanayagam, G., Board, P.G., Parker, M.W., Leisinger, T. &
Vuilleumier, S. (2001) Dichloromethane mediated in vivo selection and
functional characterization of rat glutathione S-transferase theta 1-1
variants. Eur. J. Biochem., 268, 4001-4010.
95. Lo Bello, Nuccetelli, M., Caccuri, A.M., Stella, L., Parker, M.W.,
Rossjohn, J., McKinstry, W.J., Federici, G., Polizio, F., Pedersen,
J.Z. & Ricci, G. (2001) Human glutathione transferase P1-1 and nitric
oxide carriers: a new role for an old enzyme. J. Biol. Chem., 276, 42138-42145.
96. Polekhina, G., House, C.M., Traficante, N., Mackay, J.P.,
Relaix, F., Sassoon, D.A., Parker, M.W. & Bowtell, D.D.L. (2002) The Siah
ubiquitin ligase component is structurally related to TRAF proteins and
functions in the TNF-signalling pathway. Nature Struct. Biol., 9, 68-75.
(Highlighted with News & Views segment "Degrading liaisons: Siah
structure revealed" by J.C. Reed & K.R. Ely, Nature Struct. Biol., 9, 8-10).
97. White, A.R., Multhaup, G., Galatis, D., McKinstry, W.J.,
Parker, M.W., Pipkorn, R, Beyreuther, K., Masters, C.L. & Cappai, R.
(2002) Contrasting, species-dependent modulation of copper-mediated
neurotoxicity by the Alzheimer's disease amyloid precursor protein.
J. Neurosci., 22, 365-376.
98. Allocati, N., Masulli, M., Casalone, E., Santucci, S.,
Favaloro, B., Parker, M.W. & Di Ilio, C. (2002) Glutamic acid 65 is
an essential residue for catalysis in Proteus mirabilis glutathione
S-transferase B1-1. Biochem J., 363,189-193.
99. Farrow, K.A., Lyras, D., Polekhina, G., Koutsis, K., Parker,
M.W. & Rood, J.I. (2002) Identification of essential residues of the
Erm(B) rRNA methyltransferase from Clostridium perfringens. Antimicrobial
Agents Chemother., 46, 1253-1261.
100. Caccuri, A.M., Antonini, G., Allocati, N., Di Ilio, C.,
Innocenti, F., De Maria, F., Parker, M.W., Masulli, M., Polizio, F.,
Lo Bello, M., Federici, G. & Ricci, G. (2002) Properties and utility
of the peculiar mixed disulfide in the bacterial glutathione transferase
B1-1. Biochemistry, 41, 4686-4693.
101. Cromer, B.A., Morton, C.J. & Parker, M.W. (2002) Anxiety over
GABAA receptor structure relieved by AchBP. Trends Biochem. Sci., 27, 280-287.
102. Cromer, B.A., Morton, C.J., Board, P.G. & Parker, M.W. (2002)
From glutathione transferase to pore in a CLIC. Eur. J. Biophys., 31,
356-364.
103. Caccuri, A.M., Antonini, G., Allocati, N., Di Ilio, C., Lo Bello,
M., De Maria, F., Turella, P., Parker, M.W., Masulli, M., Federici, G. &
Ricci, G. (2002) GSTB1-1 from Proteus mirabilis: a snapshot of an enzyme
in the evolutionary pathway from a redox enzyme into a conjugation
enzyme. J. Biol. Chem., 277, 18777-18784.
104. Coggan, M., Flanagan, J.U., Parker, M.W., Vichai, V., Pearson,
W.R. & Board, P.G. (2002) Identification and characterization of GSTT3,
a third murine theta class glutathione transferase. Biochem. J., 366,
323-332.
105. Tsitrin, Y., Morton, C.J., El Bez, C., Paumard, P. Velluz, M-C.,
Adrian, M., Dubochet, J., Parker, M.W., Lanzavecchia, S. &
van der Goot, F.G. (2002) Conversion of a transmembrane to a water-soluble
protein complex by a single point mutation. Nature Struct. Biol., 9,
729-733.
106. Bowser, D.N., Wagner, D.A., Czajkowski, C., Cromer, B.A.,
Parker, M.W., Wallace, R.H., Harkin, L.A., Mulley, J.C., Marini, C.,
Berkovic, S.F., Williams, D.A., Jones, M.V. & Petrou, S. (2002) Altered
kinetics and benzodiazepine sensitivity of a GABAA receptor subunit
mutation (g2-R43Q) found in human epilepsy. Proc. Natl. Acad. Sci.
USA, 99, 15170-15175.
106. Micaloni, C., Kong, G. K-W., Mazzetti, A.P., Nuccetelli, M.,
Antonini, G., Stella, L., McKinstry, W.J., Polekhina, G., Rossjohn, J.,
Federici, G., Ricci, G., Parker, M.W. & Lo Bello, M. (2003) Engineering
a new C-terminal tail in the H-site of human glutathione transferase
P1-1: structural and functional consequences. J. Mol. Biol., 325,
111-122.
107. Kong, G. K-W., Polekhina, G., McKinstry, W.J., Parker, M.W.,
Dragani, B., Aceto, A., Paludi, D., Principe, D.R., Mannervik, B. &
Stenberg, G. (2003) Contribution of glycine 146 to a conserved
folding module affecting stability and refolding of human GSTP1-1.
J. Biol. Chem., 278, 1291-1302.
108. Morton, C.J., Cameron, R., Lawrence, L.J., Lin, B., Lowe, M.,
Luttick, A., Mason, A., McKimm-Breschkin, J., Parker, M.W., Ryan, J.,
Smout, M., Tucker, S. & Young, P. (2003) Homology model of the
respiratory syncytial virus F protein: application in the structural
characterisation of fusion inhibitor escape mutants. Virology, 311,
275-288.
109. Nevin, S.T., Cromer, B.A., Haddrill, J.L., Morton, C.J.,
Parker, M.W. & Lynch, J.W. (2003) Insights into the structural basis
for zinc inhibition of the glycine receptor. J. Biol. Chem., 278,
28985-28992.
110. Polekhina, G., Gupta, A., Michell, B.M., van Denderen, B.,
Murthy, S., Feil, S.C., Jennings, I.G., Campbell, D.J., Witters, L.A.,
Parker, M.W., Kemp, B.E. & Stapleton, D. (2003) AMPK beta-subunit
targets metabolic stress-sensing to glycogen. Curr. Biol., 13, 867-871.
111. Lin, H.J., Johansson, A-S., Stenberg, G., Materi, A.M.,
Park, J.M., Dai, A., Zhou, H., Gim, J.S.Y., Kau, I.H., Hardy, S.I.,
Parker, M.W. & Mannervik, B. (2003) Naturally occurring Phe151Leu
substitution near a conserved folding module lowers stability of
glutathione transferase P1-1. Biochim. Biophys. Acta, 1649, 16-23.
112. Barnham, K., McKinstry, W.J., Multhaup, G., Galatis, D.,
Morton, C.J., Curtain, C.C., Williamson, N.A., White, A.R., Hinds, M.G.,
Norton, R.S., Beyreuther, K., Masters, C.L., Parker, M.W. & Cappai, R.
(2003) Structure of the Alzheimer's disease amyloid precursor protein
copper binding domain: a regulator of neuronal copper homeostasis.
J. Biol. Chem., 278, 17401-17407.
113. Johnston, J.M., Arcus, V.L., Morton, C.J., Parker, M.W. &
Baker, E.N. (2003) The crystal structure of a putative
methyltransferase from Mycobacterium tuberculosis: misannotation of
a genome suggested by protein structural analysis. J. Bacteriol., 185,
4057-4065.
114. Board, P.G., Taylor, M.C., Coggan, M., Parker, M.W.,
Lantum, H.B. & Anders, M.W. (2003) Clarification of the role of key active
site residues of glutathione transferase zeta/maleylacetoacetate isomerase
by a new spectrophotometric technique. Biochem. J., 374, 731-737.
115. Parker, M.W. (2003) Protein structure from X-ray diffraction.
J. Biol. Physics, 29, 341-362.
116. Parker, M.W. (2003) Cryptic clues as to how water-soluble protein
toxins form pores in membranes. Toxicon, 42, 1-6.
117. Ricci, G., Caccuri, A.M., Lo Bello, M., Parker, M.W.,
Nuccetelli, M., Turella, P., Stella, L., Di Iorio, E.E. & Federici, G.
(2003) Glutathione transferase P1-1: self-preservation of an anti-cancer
enzyme. Biochem. J., 376, 71-76.
118. Ortiz-Salmerón, E., Nuccetelli, M., Oakley, A.J.,
Parker, M.W., Lo Bello, M. & García-Fuentes, L. (2003) Thermodynamic
description of the effect of mutation Y49F on human glutathione
transferase P1-1 in binding with glutathione and the inhibitor
S-hexylglutathione. J. Biol. Chem., 278, 46938-46948.
119. Adams, J., Chen, Z-P., van Denderen, B.J.W., Morton, C.J.,
Parker, M.W., Witters, L.A., Stapleton, D. & Kemp, B.E. (2004)
Intrasteric control of AMPK via the g1 subunit AMP allosteric regulatory
site. Protein Sci., 13, 155-165.
120. Polekhina, G., Giddings, K.S., Tweten, R.K. & Parker, M.W. (2004)
Crystallization and preliminary X-ray analysis of the human specific
toxin intermedilysin. Acta Cryst., in press.
121. Melton, J., Parker, M.W., Rossjohn, J., Buckley, J.T. &
Tweten, R.K. (2004) The identification and structure of the
membrane-spanning domain of the Clostridium septicum a-toxin.
J. Biol. Chem., in press.
122. Parker, M.W. & Feil, S.C. (2004) Pore-forming protein toxins:
from structure to function. Prog. Mol. Biol. Biophys., in press.
