Alpha-1-antitrypsin (also known as α1-antitrypsin or A1AT) is an inhibitor of Elastase and Trypsin. It is a member of the Serine Protease Inhibitor (Serpin) family, and as such undergoes a conformational change where the substrate protein associates with a loop region on A1AT causing that loop to become ordered as a Beta Strand[1]. In this case Trypsin (the substrate) is inhibited when a covalent bond is formed to A1AT through the newly formed Beta region[1]. Once bound covalently to its substrate the stability of the A1AT complex goes up drasticallyCite error: Closing </ref> missing for <ref> tag.
Role in diseaseRole in disease
Mutations of MET358 to ARG can lead to a change in specificity in the Elastase binding pocket, essentially turning the M358R mutant of A1AT into a Thrombin inhibitor by generating specificity for this new substrate. This drop in Thrombin levels can lead to hemorrhaging. [2]
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ReferencesReferences
- ↑ 1.0 1.1 Nature 455, 1189-1190 (30 October 2008)
- ↑ Biochemistry, Fifth Edition, p.289.
