9ZRW

Alpha 1-AntiTrypsin (C232S) in Complex with B211421

This is a non-PDB format compatible entry.

Summary for 9ZRW

• Entry DOI: 10.2210/pdb9zrw/pdb
• Descriptor: Alpha-1-antitrypsin, N-[(1S,2R)-1-(2-chloro-3-fluorophenyl)-1-hydroxypentan-2-yl]-7-fluoro-2-oxo-2,3-dihydro-1H-indole-4-carboxamide, GLYCEROL, ... (4 entities in total)
• Functional Keywords: protease binding, peptidase inhibitor activity, inflammatory response, protein binding
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 46280.79

Authors

Kumar, G. (deposition date: 2025-12-21, release date: 2026-10-28)

Primary citation

Handyside, B.,Wenzel, H.,Mackenzie, D.,Chang, C.,Greenslade, A.,Van Vleet, J.,Heglar, B.,Chen, J.C.,Zhang, L.,Larimore, K.,Zhou, H.,Trantcheva, I.,Sims, L.,Evans, K.,Fong, S.,Kumar, G.,Annu, K.,Ronzoni, R.,Irving, J.A.,Wang, B.,Bunting, S.,Lomas, D.A.
BMN 349, a small molecule inhibitor of Z alpha-1 antitrypsin polymerization, increases secretion and reduces intrahepatic inclusions in a mouse model of disease.
Hepatology, 2026

PubMed Abstract: Alpha-1 antitrypsin (AAT), encoded by the SERPINA1 gene, is primarily synthesized in the liver and secreted into the blood. The SERPINA1 Z allele encodes Z-AAT (Glu342Lys), a variant that self-associates into polymers that are retained in hepatocytes and trigger inflammation and hepatic injury. Targeting and preventing Z-AAT polymerization allows a therapy to directly address the pathophysiology of AAT deficiency (AATD) associated liver disease.

PubMed: 42065867
DOI: 10.1097/HEP.0000000000001778

Experimental method

X-RAY DIFFRACTION (1.87 Å)