1IZ2

Interactions causing the kinetic trap in serpin protein folding

Summary for 1IZ2

• Entry DOI: 10.2210/pdb1iz2/pdb
• Descriptor: alpha1-antitrypsin, alpha-D-glucopyranose-(1-2)-(5R)-5-[(2R)-2-hydroxynonyl]-beta-D-xylulofuranose (3 entities in total)
• Functional Keywords: serpin, folding, antitrypsin, protein binding
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 44657.63

Authors

Im, H.,Woo, M.-S.,Hwang, K.Y.,Yu, M.-H. (deposition date: 2002-09-19, release date: 2003-02-11, Last modification date: 2023-12-27)

Primary citation

Im, H.,Woo, M.-S.,Hwang, K.Y.,Yu, M.-H.
Interactions causing the kinetic trap in serpin protein folding
J.BIOL.CHEM., 277:46347-46354, 2002

PubMed Abstract: Conformational transition is fundamental to the mechanism of functional regulation in proteins, and serpins (serine protease inhibitors) can provide insight into this process. Serpins are metastable in their native forms, and they ordinarily undergo conformational transition to a stable state only when they form a tight complex with target proteases. The metastable native form is thus considered to be a kinetically trapped folding intermediate. We sought to understand the nature of the serpin kinetic trap as a step toward discovering how conformational transition is regulated. We found that mutations of the B/C beta-barrel of native alpha(1)-antitrypsin, a prototypical serpin, allowed conversion of the molecule into a more stable state. A 2.2 A resolution crystal structure of the stable form (PDB code, ) showed that the reactive site loop is inserted into an A beta-sheet, as in the latent plasminogen activator inhibitor-1. Mutational analyses suggest strongly that interactions not found in the final stable form cause the kinetic trap in serpin protein folding.

PubMed: 12244055
DOI: 10.1074/jbc.M207682200

Experimental method

X-RAY DIFFRACTION (2.2 Å)