4DTE
Crystal structure of zebrafish plasminogen activator inhibitor-1 (PAI-1)
Summary for 4DTE
| Entry DOI | 10.2210/pdb4dte/pdb |
| Descriptor | Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | active serpin, hydrolase inhibitor, zebarfish upa |
| Biological source | Danio rerio (leopard danio,zebra danio,zebra fish) |
| Total number of polymer chains | 2 |
| Total formula weight | 84514.34 |
| Authors | Johansen, J.S. (deposition date: 2012-02-21, release date: 2013-03-27, Last modification date: 2024-11-27) |
| Primary citation | Bager, R.,Johansen, J.S.,Jensen, J.K.,Stensballe, A.,Jendroszek, A.,Buxbom, L.,Sorensen, H.P.,Andreasen, P.A. Protein conformational change delayed by steric hindrance from an N-linked glycan. J.Mol.Biol., 425:2867-2877, 2013 Cited by PubMed Abstract: Very few studies have attributed a direct, active, functional role to N-linked glycans. We describe here an N-linked glycan with a unique role for maintaining the active conformation of a protein of the serpin family. The distinguishing feature of serpins is the "stressed-to-relaxed" transition, in which the reactive center loop inserts as a β-strand into the central β-sheet A. This transition forms the basis for the conversion of serpins to the inactive latent state. We demonstrate that plasminogen activator inhibitor-1 (PAI-1) from zebrafish converts to the latent state about 5-fold slower than human PAI-1. In contrast to human PAI-1, fish PAI-1 carries a single N-linked glycan at Asn185 in the gate region through which the reactive center loop passes during latency transition. While the latency transition of human PAI-1 is unaffected by deglycosylation, deglycosylated zebrafish PAI-1 (zfPAI-1) goes latent about 50-fold faster than the glycosylated zfPAI-1 and about 25-fold faster than non-glycosylated human PAI-1. X-ray crystal structure analysis of glycosylated fish PAI-1 confirmed the presence of an N-linked glycan in the gate region and a lack of glycan-induced structural changes. Thus, latency transition of zfPAI-1 is delayed by steric hindrance from the glycan in the gate region. Our findings reveal a previously unknown mechanism for inhibition of protein conformational changes by steric hindrance from N-linked glycans. PubMed: 23702291DOI: 10.1016/j.jmb.2013.05.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.96 Å) |
Structure validation
Download full validation report
