1DVM

ACTIVE FORM OF HUMAN PAI-1

Summary for 1DVM

• Entry DOI: 10.2210/pdb1dvm/pdb
• Related: 1A7C 1B3K 1C5G 1DB2 1DVN
• Descriptor: PLASMINOGEN ACTIVATOR INHIBITOR-1, CHLORIDE ION (3 entities in total)
• Functional Keywords: serpin, pai-1, inhibitor, blood clotting
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P05121
• Total number of polymer chains: 4
• Total formula weight: 171322.08

Authors

Stout, T.J.,Graham, H.,Buckley, D.I.,Matthews, D.J. (deposition date: 2000-01-21, release date: 2000-09-06, Last modification date: 2024-02-07)

Primary citation

Stout, T.J.,Graham, H.,Buckley, D.I.,Matthews, D.J.
Structures of active and latent PAI-1: a possible stabilizing role for chloride ions.
Biochemistry, 39:8460-8469, 2000

PubMed Abstract: Serpins exhibit a range of physiological roles and can contribute to certain disease states dependent on their various conformations. Understanding the mechanisms of the large-scale conformational reorganizations of serpins may lead to a better understanding of their roles in various cardiovascular diseases. We have studied the serpin, plasminogen activator inhibitor 1 (PAI-1), in both the active and the latent state and found that anionic halide ions may play a role in the active-to-latent structural transition. Crystallographic analysis of a stable mutant form of active PAI-1 identified an anion-binding site between the central beta-sheet and a small surface domain. A chloride ion was modeled in this site, and its identity was confirmed by soaking crystals in a bromide-containing solution and calculating a crystallographic difference map. The anion thus located forms a 4-fold ligated linchpin that tethers the surface domain to the central beta-sheet into which the reactive center loop must insert during the active-to-latent transition. Timecourse experiments measuring active PAI-1 stability in the presence of various halide ions showed a clear trend for stabilization of the active form with F(-) > Cl(-) > Br(-) >> I(-). We propose that the "stickiness" of this pin (i.e., the electronegativity of the anion) contributes to the energetics of the active-to-latent transition in the PAI-1 serpin.

PubMed: 10913251
DOI: 10.1021/bi000290w

Experimental method

X-RAY DIFFRACTION (2.4 Å)