| Autor: |
Urvashi Sharma, Sandrine Vadon-Le Goff, Karl Harlos, Yuguang Zhao, Natacha Mariano, Cecile Bijakowski, Jean-Marie Bourhis, Catherine Moali, David J.S. Hulmes, NUSHIN BANU AGHAJARI |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-1719973/v1 |
| Popis: |
Sizzled (Szl) is both a secreted frizzled related protein (sFRP) and a naturally occurring inhibitor of the zinc metalloproteinase bone morphogenetic protein-1 (BMP-1), a key regulator of extracellular matrix assembly and growth factor activation. Here we present a new crystal structure for Szl which differs from that previously reported by a large scale (90°) hinge rotation between its cysteine-rich and netrin-like domains. We also present results of a molecular docking analysis showing interactions likely to be involved in the inhibition of BMP-1 activity by Szl. When compared with known structures of BMP-1 in complex with small molecule inhibitors, this reveals features that may be helpful in the design of new inhibitors to prevent the excessive accumulation of extracellular matrix that is the hallmark of fibrotic diseases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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