Associate Professor Bostjan Kobe, Department of Biochemistry and Molecular Biology, School of Molecular and Microbial Sciences, University of Queensland.
Brief CV:
A/Prof Kobe has made a number of high impact contributions to the field
of structural biology, on several different biological systems. One
outstanding contribution involves the solenoid protein structures
(proteins built of structural repeats assembled in a superhelical fashion)
that are generally involved in protein-protein interactions; he determined
the first 3D structure of a protein built entirely from sequence repeats
(ribonuclease inhibitor (RI), a protein with leucine-rich repeats (LRRs)
(Kobe and Deisenhofer, 1993). It allowed him to identify unique features of
LRR- and other solenoid proteins that make these proteins extremely effective
in forming protein-protein interactions in a variety of cellular processes
(Kobe and Deisenhofer, 1994), as further demonstrated when he determined the
first structure of an LRR protein bound to its ligand, the RI-RNase A
structure (Kobe and Deisenhofer, 1995). Another major contribution involves
the mechanism of active site-directed (intrasteric) protein regulation;
his structural work on a number of proteins including protein kinase
twitchin (Kobe et al, 1996; Heierhorst et al, 1996), the metabolic enzyme
phenylalanine hydroxylase (Kobe et al, 1999) and nuclear transport factor
importin-alpha (Kobe, 1999) established intrasteric regulatory mechanisms
in these proteins and revealed the broad scope of this regulation in a
number of proteins and cellular processes (Kobe and Kemp, 1999). A recent
high impact contribution involves the development of bioinformatic tools for
the analysis of sequence-specific protein-protein interactions in signalling
pathways; the group have developed a structure-based method that predicts an
optimal hexapeptide phosphorylation motif using only the sequence of the
kinase as input (Brinkworth et al, 2003). several contributions have been
made on the technical aspects of structural biology techniques.
The crystal structure
determination of the human T-cell leukemia virus type 1 (HTLV-1) gp21
(Kobe et al, 1999) led to the development of a novel strategy for
crystallization and crystal structure determination; as world first, Kobe's
group crystallized this protein as a chimera with maltose-binding protein (MBP)
using a short linker between the partners, and used the known structure of
MBP in molecular replacement to solve the structure. Many other investigators
have now adopted this strategy to determine the crystal structures of
several novel proteins (Smyth et al, 2003). A/Prof Kobe was also involved
in one of the first applications of cryocrystallography on integral membrane
protein crystals of FepA (Smith et al, 1998), and one of the first
applications of NMR to the study of polypeptides in membrane-mimetic
environments, specifically examining the conformational behaviour of
signal peptides in detergent micelles (Rizo et al, 1993).
International linkages:
USA, UK, Brazil, Slovenia, Germany, Denmark.
Students and postdocs likely to be involved in or use the Network:
Postdocs:
Ross Brinkworth
Pawel Listwan
PhD Students:
Robert Serek
Thorsten Kampmann
Sundy Yang
Relevant grants
| 2001-2003 | Structural studies of plant disease resistance proteins, Kobe, Anderson, Ellis. $318,000 |
| 2004-2006 | Structure and function of novel macrophage proteins using high throughput crystallography, Martin, Kobe. $600,000 |
| 2003-2007 | NHMRC Fellowship, Kobe, $600,000 |
| 2003-2005 | Molecular basis of Dengue Virus-induced fusion, Young, Kobe. $360,000. |
| 2004 | Structural biology of macromolecular assemblies as part of the Visual Cell program, Kobe. $10,000 |
Relevant publications:
Book chapters:
1. Kobe, B., Gleichmann, T., Teh, T., Heierhorst, J., and Kemp, B.E.
(1999). Crystallization of protein kinases and phosphatases. In Protein
phosphorylation: A practical approach. Second Edition. Edited by D.G.
Hardie. Oxford University Press, Oxford, UK, pp 387-421.
2. Heierhorst, J., Pearson, R.B., Horne, J., Bozinovski, S., Kobe, B.
and Kemp, B.E. (2000). Protein serine/threonine kinases. In Principles of
Molecular Regulation. Conn, P.M. and Means, A.R. (Eds). Humana Press,
Totowa, New Jersey. ISBN: 0-89603-630-8, Chapter 17, pp. 297-310.
3. Brinkworth, R.I., Breinl, R. and Kobe, B. (2002). Conserved
sequence motifs in protein kinase families. In Recent Research Developments
in Protein Folding, Stability and Design. Edited by M.M. Gromiha and
S. Selvaraj. Research Signpost 37/661 (2), Trivandrum 695 023, Kerala,
India, pp. 67-77.
4. Kobe, B., Jennings, I.G. and Cotton, R.G.H. (2002). Structure and
regulation of phenylalanine hydroxylase, and implications for related
enzymes. In Chemistry and Biology of Pteridines and Folates. Edited by
S. Milstien, G. Kapatos, R. A. Levine and B. Shane, Kluwer Academic
Publishers, Norwell, Massachusetts, USA, pp. 79-84.
5. Brinkworth, R.I., Kobe, B. and Kemp, B.E. (2003) Peptide substrates
of cyclic nucleotide-dependent protein kinases. In Handbook of Cell
Signaling. Edited by R. A. Bradshaw and E. Dennis. Academic Press,
San Diego, California, USA. Vol. 2, Ch. 202, pp. 495-499.
6. Kobe, B. and Kemp, B.E. (2003). Principles of kinase regulation.
In Handbook of Cell Signaling. Edited by R. A. Bradshaw and E. Dennis.
Academic Press, San Diego, California, USA. Vol. 1, Ch. 89, pp. 539-542.
Journal articles:
1. Teh, T., Tiganis, T., and Kobe, B. (1999). Crystallization of
importin alpha, the nuclear import receptor. Acta Crystallogr. D Biol.
Crystallogr. 55, 561-563 (Impact factor 2.0, 3 citations).
2. Kobe, B., Jennings, I.G., House, C.M., Michell, B.J., Goodwill, K.E.,
Santarsiero, B.D., Stevens, R.C., Cotton, R.G.H., and Kemp, B.E. (1999).
Structural basis of autoregulation of phenylalanine hydroxylase.
Nature Struct. Biol. 6, 442-448 (Impact factor 10.2, 67 citations).
3. Kobe, B. (1999). Autoinhibition by an internal nuclear localization
signal revealed by the crystal structure of mammalian importin alpha.
Nature Struct. Biol. 6, 388-397 (Impact factor 10.2, 58 citations).
4. Kobe, B., Center, R.J., Kemp, B.E., and Poumbourios, P. (1999).
Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain
crystallized as a maltose-binding protein chimera reveals structural
evolution of retroviral transmembrane proteins. Proc. Natl. Acad. Sci. USA.
96, 4319-4324 (Impact factor 10.7, 61 citations).
5. Kobe, B., Gleichmann, T., Horne, J., Jennings, I.G., Scotney, P.D.,
and Teh, T. (1999). Turn up the HEAT. Structure 7, R91-R97 (Impact factor
6.0, 14 citations).
6. Poumbourios, P., Center, R.J., Wilson, K.A., Kemp, B.E., and
Kobe, B. (1999). Evolutionary conservation of the membrane fusion machine.
IUBMB Life 48, 151-156 (Impact factor 1.8, 3 citations).
7. Kobe, B. and Kemp, B.E. (1999). Active-site directed protein regulation.
Nature 402, 373-376 (Impact factor 30.4, 35 citations).
8. Montgomery, J., Ilg, T., Thompson, J.K., Kobe, B. and Handman,
E. (2000). Identification and predicted structure of a leucine-rich repeat
motif shared by Leishmania major proteophosphoglycan and Parasite
Surface Antigen 2. Mol. Biochem. Parasitol. 107, 289-295 (Impact factor
2.9, 7 citations).
9. Fontes, M.R.M., Teh, T. and Kobe, B. (2000). Structural basis of
recognition of monopartite and bipartite nuclear localization sequences by
mammalian importin-alpha. J. Mol. Biol. 297, 1183-1194 (Impact factor 5.4,
42 citations).
10. Hammet, A., Pike, B.L., Mitchelhill, K.I., Teh, T., Kobe, B., House,
C.M., Kemp, B.E., and Heierhorst, J. (2000). FHA domain boundaries of the
Dun1p and Rad53p cell cycle checkpoint kinases. FEBS Lett. 471, 141-146
(Impact factor 3.9, 18 citations).
11. Jennings, I.G., Cotton, R.G.H. and Kobe, B. (2000). Structural
interpretation of mutations in phenylalanine hydroxylase protein aids in
identifying genotype-phenotype correlations in phenylketonuria. Eur. J.
Hum. Genet. 8, 683-696 (Impact factor 3.1, 10 citations).
12. Maerz, A.L., Center, R.J., Kemp, B.E., Kobe, B. and Poumbourios,
P. (2000). Functional implications of the human T-lymphotropic virus
type 1 transmembrane glycoprotein helical hairpin structure. J. Virol. 74,
6614-6621 (Impact factor 5.2, 7 citations).
13. Kobe, B. and Kajava, A.V. (2000). When protein folding is
simplified to protein coiling: the continuum of solenoid protein
structures. Trends Biochem. Sci. 25, 509-515 (Impact factor 14.4,
25 citations).
14. Jennings, I.G., Cotton, R.G.H. and Kobe, B. (2000). Functional
analysis, using in vitro mutagenesis, of amino acids located in the
phenylalanine hydroxylase active site. Arch. Biochem. Biophys. 384,
238-244 (Impact factor 2.6, 6 citations).
15. Kobe, B. (2001). Crystallization and crystal structure determination
of ribonuclease A- ribonuclease inhibitor protein complex.
Methods Mol. Biol. 160: 201-211
16. Jennings, I.G., Teh, T. and Kobe, B. (2001). Essential role of the
N-terminal autoregulatory sequence in the regulation of phenylalanine
hydroxylase. FEBS Lett. 488, 196-200 (Impact factor 3.9, 11 citations).
17. *Blanchard, H., Fontes, M.R.M., Hammet, A., Pike, B.L., Teh, T.,
Gleichmann, T., Gooley, P.R., Kobe, B. and Heierhorst, J. (2001).
Crystallization and preliminary X-ray diffraction studies of FHA domains
of Dun1 and Rad53 protein kinases. Acta Crystallogr. D Biol. Crystallogr. 57,
459-461 (Impact factor 2.0).
18. *Catimel, B., Teh, T., Fontes, M.R.M., Jennings, I.G., Jans, D.A.,
Howlett, G.J., Nice, E.C. and Kobe, B. (2001). Biophysical characterization
of interactions involving importin-alpha during nuclear import.
J. Biol. Chem. 276, 34189-34198 (Impact factor 6.7, 24 citations).
19. Kobe, B. and Kajava, A.V. (2001). The leucine-rich repeat (LRR) as
a protein recognition motif. Curr. Opin. Struct. Biol. 11, 725-732 (Impact
factor 9.6, 68 citations).
20. Brinkworth, R.I., Horne, J. and Kobe, B. (2002). A computational
analysis of substrate binding strength by phosphorylase kinase and
protein kinase A. J. Mol. Recognit. 15, 104-111 (Impact factor 2.8, 1
citation).
21. Kajava, A.V. and Kobe, B. (2002). Assessment of the ability to
model proteins with leucine-rich repeats in light of the latest
structural information. Protein Sci. 11, 1082-1090 (Impact factor 3.5,
14 citations).
22. Kobe, B. (2002). Intramolecular autoregulatory sequences in
proteins. Croatica Chemica Acta 75, 805-816 (Impact factor 0.7).
23. Horne, J., Jennings, I.G., Teh, T., Gooley, P.R. and Kobe, B.
(2002). Structural characterization of the N-terminal autoregulatory
sequence of phenylalanine hydroxylase. Protein Sci., 11, 2041-2047
(Impact factor 3.5, 1 citation).
24. Brinkworth, R.I, Breinl, R.A. and Kobe, B. (2003). Structural
basis and prediction of substrate specificity in protein
serine/threonine kinases. Proc. Natl. Acad. Sci. USA 100, 74-79
(Impact factor 10.7, 5 citations).
25. *Wooh, J.W., Kidd, R.D., Martin, J.L. and Kobe, B. (2003)
Comparison of three commercial sparse matrix crystallisation screens.
Acta Crystallogr. D Biol. Crystallogr. 59, 769-772 (Impact factor 2.0).
26. Smyth, D.R., Mrozkiewicz, M.K., McGrath, W.J., Listwan, P. and
Kobe, B. (2003) Crystal structures of fusion proteins with large
affinity tags. Protein Sci., 12, 1313-1322 (Impact factor 3.5).
27. *Fontes, M.R., Teh, T., Jans, D.A,. Brinkworth, R.I. and
Kobe, B. (2003) Structural basis for the specificity of bipartite
nuclear localization sequence binding by importin-alpha.
J. Biol. Chem. 278, 27981-27987 (Impact factor 6.7, 3 citations).
28. Fontes, M.R., Teh, T., Toth, G., John, A., Pavo, I.,
Jans, D.A. and Kobe, B. (2003) The role of flanking sequences and
phosphorylation in the recognition of SV40 large T-antigen
nuclear localisation sequence by importin-alpha. Biochem. J. 375,
339-349 (Impact factor 4.6).
29. Kobe, B. (2003) Protein regulation, protein-protein
interactions and structural genomics. Acta Chim. Slov. 50, 547-562
(Impact factor 0.5) \
Ten career-best publications
1. Kobe, B. and Deisenhofer, J. (1993). Crystal structure of porcine
ribonuclease inhibitor, a protein with leucine-rich repeats. Nature 366,
751-756 (Impact factor 30.4, 334 citations).
2. Kobe, B. and Deisenhofer, J. (1995) A structural basis of the
interactions between leucine-rich repeats and protein ligands. Nature 374,
183-186 (Impact factor 30.4, 297 citations).
3. Heierhorst, J., Kobe, B., Feil, S.C., Parker, M.W., Benian, G.M.,
Weiss, K.R. and Kemp, B.E. (1996). Ca2+/S100 regulation of giant protein
kinases. Nature 380, 636-639 (Impact factor 30.4, 85 citations).
4. Kobe, B., Heierhorst, J., Feil, S.C., Parker, M.W., Benian, G.M.,
Weiss, K.R. and Kemp, B.E. (1996). Giant protein kinases: domain
interactions and structural basis of autoregulation. EMBO J. 15,
6810-6821 (Impact factor 10.7, 36 citations).
5. Kobe, B. (1996). Leucines on a roll. Nature Struct. Biol. 3,
977-980 (Impact factor 10.2, 17 citations).
6. Kobe, B., Jennings, I.G., House, C.M., Michell, B.J.,
Goodwill, K.E., Santarsiero, B.D., Stevens, R.C., Cotton, R.G.H.,
and Kemp, B.E. (1999). Structural basis of autoregulation of
phenylalanine hydroxylase. Nature Struct. Biol. 6, 442-448 (Impact factor 10.2,
67 citations).
7. Kobe, B. (1999). Autoinhibition by an internal nuclear localization
signal revealed by the crystal structure of mammalian importin alpha.
Nature Struct. Biol. 6, 388-397 (Impact factor 10.2, 58 citations).
8. Kobe, B., Center, R.J., Kemp, B.E., and Poumbourios, P. (1999).
Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain
crystallized as a maltose-binding protein chimera reveals structural evolution
of retroviral transmembrane proteins. Proc. Natl. Acad. Sci. USA. 96,
4319-4324 (Impact factor 10.7, 61 citations).
9. Kobe, B. and Kemp, B.E. (1999). Active-site directed protein
regulation. Nature 402, 373-376 (Impact factor 30.4, 35 citations).
10. Brinkworth, R.I, Breinl, R.A. and Kobe, B. (2003). Structural
basis and prediction of substrate specificity in protein serine/threonine
kinases. Proc. Natl. Acad. Sci. USA 100, 74-79 (Impact factor 10.7, 5 citations).
