Structure Of Tumor Necrosis Factor-Alpha-Converting Enzyme Solved - Milestone Toward Rational Drug Design For Rheumatoid Arthritis And Endot...( nd multiple wavelengths diffraction (MA...)

nd multiple wavelengths diffraction (MAD) methods at the DESY/Hamburg (Dr. Hans Bartunik).

The results of this study have now been published by Maskos et.al. in the Proceedings of the National Academy of Sciences, USA (1998), 95 (7), 3408-3412. This structure reveals some topological similarities with the catalytic domain of a snake venom metalloproteinase previously elucidated by the same Martinsried group, with a number of large polypeptide insertion loops generating unique features at the molecular surface, however. The active site region of the TACE molecule also shares properties with the matrix metalloproteinases (to which collagenases, gelatinases and stromelysins belong), but differs considerably in its substrate binding features. The structure of the human necrosis factor-a-converting enzyme helps to explain the specific capability of TACE to cleave proTNFa, but also provides the structural basis for the rational design of specific inhibitors, which could selectively impair the catalytic action of TACE.

The TACE structure thus opens a new approach toward the structure-based design of specific synthetic TACE inhibitors. Such tailored inhibitors could act as effective therapeutic agents against arthritic lesions and might increase the rate of survival in various endotoxin-induced septic shock syndromes.

'"/>

Contact: Wolfram Bode
bode@biochem.mpg.de
+49-89-8578 2676
Max-Planck-Gesellschaft
6-Apr-1998


Page: 1 2
Related biology news :

1. Structure solved at Scripps shows how one human protein reduces potency of chemotherapy
2. Structure solved by Scripps scientists shows one way that body controls gene expression
3. Structure of a Nobel-prize winning molecule: Aquaporin
4. Structure of HIV-neutralizing antibody solved
5. Structure of key breast cancer receptor determined
6. Structure of cog at the hub of metabolism reveals anti-ageing function
7. Structure of pain-modulating enzyme described by scientists at the Scripps Research Institute
8. Structure reveals details of cells cargo-carriers
9. Structure of key receptor unlocked; Related proteins will fall like dominoes
10. New Science Press launches Proteins: From Sequence to Structure
11. Third piece completes deadly puzzle: Structure of anthrax toxin offers clues to treatment