PDBsum entry 1sek

Serine protease inhibitor

PDB id: 1sek

Contents

Protein chain

376 a.a. *

Waters ×345

* Residue conservation analysis

PDB id:

1sek

Name:

Serine protease inhibitor

Title:

The structure of active serpin k from manduca sexta and a model for serpin-protease complex formation

Structure:

Serpin k. Chain: a. Engineered: yes

Source:

Manduca sexta. Tobacco hornworm. Organism_taxid: 7130. Tissue: hemolymph. Cellular_location: extracellular. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Monomer (from PDB file)

Resolution:

2.10Å R-factor: 0.199 R-free: 0.260

Authors:

J.Li,Z.Wang,B.Canagarajah,H.Jiang,M.Kanost,E.J.Goldsmith

Key ref:

J.Li et al. (1999). The structure of active serpin 1K from Manduca sexta. Structure, 7, 103-109. PubMed id: 10368276 DOI: 10.1016/S0969-2126(99)80013-6

Date:

06-Mar-98 Release date: 23-Mar-99

Protein chain

Q25526  (Q25526_MANSE) -  Serine protease inhibitor from Manduca sexta

Seq: 392 a.a.

Struc: 376 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/S0969-2126(99)80013-6

Structure 7:103-109 (1999)

PubMed id: 10368276

The structure of active serpin 1K from Manduca sexta.

J.Li, Z.Wang, B.Canagarajah, H.Jiang, M.Kanost, E.J.Goldsmith.

ABSTRACT

BACKGROUND: The reactive center loops (RCL) of serpins undergo large conformational changes triggered by the interaction with their target protease. Available crystallographic data suggest that the serpin RCL is polymorphic, but the relevance of the observed conformations to the competent active structure and the conformational changes that occur on binding target protease has remained obscure. New high-resolution data on an active serpin, serpin 1K from the moth hornworm Manduca sexta, provide insights into how active serpins are stabilized and how conformational changes are induced by protease binding. RESULTS: The 2.1 A structure shows that the RCL of serpin 1K, like that of active alpha1-antitrypsin, is canonical, complimentary and ready to bind to the target protease between P3 and P3 (where P refers to standard protease nomenclature),. In the hinge region (P17-P13), however, the RCL of serpin 1K, like ovalbumin and alpha1-antichymotrypsin, forms tight interactions that stabilize the five-stranded closed form of betasheet A. These interactions are not present in, and are not compatible with, the observed structure of active alpha1-antitrypsin. CONCLUSIONS: Serpin 1K may represent the best resting conformation for serpins - canonical near P1, but stabilized in the closed conformation of betasheet A. By comparison with other active serpins, especially alpha1-antitrypsin, a model is proposed in which interaction with the target protease near P1 leads to conformational changes in betasheet A of the serpin.

Selected figure(s)

Figure 5.
Figure 5. The RCL of serpin 1K. (a) Stereo diagram showing interactions of the hinge (P[17]–P[13]) in the RCL with ts3AhF1, thDs2A, and ts2Bs3B. Water molecules are shown as cyan spheres. (b) Ribbon diagram corresponding to (a).

The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 103-109) copyright 1999.

Figure was selected by an automated process.