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Professor Wolfram Bode

Max-Planck-Institute for Biochemistry
82152 Martinsried, Germany
Email: bode@biochem.mpg.de
Tel: +49 89 8578 2676
Fax: +49 89 8578 3516
Homepage: http://www.biochem.mpg.de/xray/load_members.html

Our work is mainly aimed at elucidating structure-function relationships of all kinds of proteinases. Our main approach is to prepare proteins of interest in the amounts required for crystallization using recombinant techniques or natural sources, to crystallize these proteins, to improve these crystals by humidity control if necessary, to collect native or MAD X-ray data inhouse and/or at the synchrotron at DESY/Hamburg, to determine the crystal structures by isomorphous or molecular replacement techniques, and to characterize the molecular structures. We are particularly interested in elucidating the mechanisms of proteinase activation, modification and inhibition, and to understand the various modes in which these proteinases recognize their specific substrates. Because several of the proteinases addressed are involved in diseases, we provide data for and are engaged in the rational design of specific inhibitors/drugs.
We have determined the crystal structures of trypsin-like serine proteinases (such as trypsin, tissue kallikreins, the granzymes, b- and a-tryptases) and their inhibitors (such as kunins, Kazal-type and Bowman-Birk-inhibitors, eglins, MPI/SLPI, and serpins) and complexes; of a,b-hydrolases such as the dipeptidyl peptidase IV; of monozinc endopeptidases (astacin, various MMPs, ADAMs) and their inhibitors (TIMPs) and complexes; of cysteine proteinases such as cathepsin B, m-calpain, pro-caspases and their physiological inhibitors; of furin and related prohormon/proprotein convertases; and of bacterial proteinases such as subtilisin Carlsberg, kumamolisin, gingipain R and the bizinc exopeptidases pepV and isoaspartyl dipeptidase. Our main focus has been on coagulation factors such as thrombin and its complexes with synthetic as well as protein inhibitors (hirudin, rhodniin, ornithodorin, triabin, haemadin), activators (staphylocoagulase), modifiers (thrombomodulin) and substrates (FPA), and on factors such as FIXa, FXa, aPC, FVIIa, FVa; on fibrinolytic factors such as m-plasmin, t-PA, uPA, vb-PA, TSVPA and complexes; and on metzincins such as astacin and the MMPs and their complexes. Currently we are particularly interested in the substrate recognition of MMPs and in the domain organization of ADAMs.
1) K. Bauer/Hannover
2) R. Black/Seattle
3) C.P. Blobel/New York
4) P. E. Bock/Nashville
5) H. Brandstetter/Martinsried
6) R. Camire/Philadelphia
7) H.-U. Demuth/Halle
8) J.-M. Foidart/Liege
9) C. Haass/Munich
10) Y. Itoh/London
11) S. Iwanaga/Kumamoto
12) W.H. Kane/Durham
13) I. Lindberg/New Orleans
14) G. Murphy/Cambridge
15) H. Nagase/London
16) K. Oda/Kyoto
17) C.M. Overall/Vancouver
18) D. Pei/Minneapolis
19) N. Schechter/Philadelphia
20) C. Sommerhoff/Munich
21) W. Stoecker/Muenster
Friedrich, R., Panizzi, P., Fuentes-Prior, P., Richter, K., Verhamme, I., Anderson, P.J., Kawabata, S., Huber, R., Bode, W., Bock, P.E. (2003) Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation. Nature 425, 535-539.

Henrich S, Cameron A, Bourenkov GP, Kiefersauer R, Huber R, Lindberg I, Bode W, Than ME. (2003) The crystal structure of the proprotein processing proteinase furin explains its stringent specificity. Nature Struct Biol. 10, 520-526.

Engel M, Hoffmann T, Wagner L, Wermann M, Heiser U, Kiefersauer R, Huber R, Bode W, Demuth HU, Brandstetter H. (2003) The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism. Proc Natl Acad Sci U S A. 100, 5063-5068.

Marquardt U, Zettl F, Huber R, Bode W, Sommerhoff C. (2002) The Crystal Structure of Human alpha1-Tryptase Reveals a Blocked Substrate-binding Region. J Mol Biol. 321, 491-502.

Fuentes-Prior, P., Iwanaga, Y., Huber, R., Pagila, R., Rummenik, G., Seto, M., Morser, J., Light, D.R. & Bode, W. (2000) Structural basis for the anticoagulant activity of the thrombin-thrombomodulin complex. Nature 404, 518-525.

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