Grants and Contracts Details
Description
We have continued to investigate conditions for determining the
structure of neurolysin complexed with a substrate or substrate analogue. Although the
original crystal form under standard crystallization conditions failed toforro complex
crystals in the past, we repeated these experiments with new inhibitors. Other systerrm
have shown the cocrystals mayor may not form depending on the particular inhibitor in
question. Factors such as inhibitor solubility in crystallization conditions, effect of inhibitor
binding on protein conformation and the stability of the inhibitor may explain why some
cocrystallize while others fail to do so. We received 6 new phosphinic inhibitors with
different amino acid sequences from our new collaborators, Dr. Vincent Dive and Dr. Juri
Jiracek. We have also received a proprietary inhibitor from a pharmaceutical company
which is likely to inhibit neurolysin by a mechanism different from that of the phosphinic
inhibitors. Whereas the phosphinic inhibitors have been shown in other zinc
nietallopeptidases to coordinate to the catalytic zinc, the proprietary inhibitor binds
elsewhere. Crystals grown in molar excess of these inhibitors were taiken to the
Advanced Photon Source for data collectilon..
Status | Finished |
---|---|
Effective start/end date | 5/22/03 → 4/30/04 |
Funding
- National Institute on Drug Abuse: $42,580.00
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