PDBsum entry 1sek

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Serine protease inhibitor PDB id
Protein chain
376 a.a. *
Waters ×345
* Residue conservation analysis
PDB id:
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)
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
06-Mar-98     Release date:   23-Mar-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q25526  (Q25526_MANSE) -  Serine protease inhibitor
392 a.a.
376 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular space   1 term 


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.
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.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20851714 C.An, E.J.Ragan, and M.R.Kanost (2011).
Serpin-1 splicing isoform J inhibits the proSpätzle-activating proteinase HP8 to regulate expression of antimicrobial hemolymph proteins in Manduca sexta.
  Dev Comp Immunol, 35, 135-141.  
19435496 A.Mulenga, R.Khumthong, and K.C.Chalaire (2009).
Ixodes scapularis tick serine proteinase inhibitor (serpin) gene family; annotation and transcriptional analyses.
  BMC Genomics, 10, 217.  
19394412 C.Suwanchaichinda, and M.R.Kanost (2009).
The serpin gene family in Anopheles gambiae.
  Gene, 442, 47-54.  
19150649 Z.Zou, Z.Picheng, H.Weng, K.Mita, and H.Jiang (2009).
A comparative analysis of serpin genes in the silkworm genome.
  Genomics, 93, 367-375.  
18060440 T.H.Roberts, and J.Hejgaard (2008).
Serpins in plants and green algae.
  Funct Integr Genomics, 8, 1.  
  19164889 D.Belorgey, P.Hägglöf, S.Karlsson-Li, and D.A.Lomas (2007).
Protein misfolding and the serpinopathies.
  Prion, 1, 15-20.  
15695806 Y.Tong, H.Jiang, and M.R.Kanost (2005).
Identification of plasma proteases inhibited by Manduca sexta serpin-4 and serpin-5 and their association with components of the prophenol oxidase activation pathway.
  J Biol Chem, 280, 14932-14942.  
15695807 Y.Tong, and M.R.Kanost (2005).
Manduca sexta serpin-4 and serpin-5 inhibit the prophenol oxidase activation pathway: cDNA cloning, protein expression, and characterization.
  J Biol Chem, 280, 14923-14931.  
15199957 M.R.Kanost, H.Jiang, and X.Q.Yu (2004).
Innate immune responses of a lepidopteran insect, Manduca sexta.
  Immunol Rev, 198, 97.  
12871289 J.A.Huntington (2003).
Mechanisms of glycosaminoglycan activation of the serpins in hemostasis.
  J Thromb Haemost, 1, 1535-1549.  
12682008 M.Wilczynska, S.Lobov, P.I.Ohlsson, and T.Ny (2003).
A redox-sensitive loop regulates plasminogen activator inhibitor type 2 (PAI-2) polymerization.
  EMBO J, 22, 1753-1761.  
11546761 L.Jankova, S.J.Harrop, D.N.Saunders, J.L.Andrews, K.C.Bertram, A.R.Gould, M.S.Baker, and P.M.Curmi (2001).
Crystal structure of the complex of plasminogen activator inhibitor 2 with a peptide mimicking the reactive center loop.
  J Biol Chem, 276, 43374-43382.
PDB code: 1jrr
11685246 S.Ye, A.L.Cech, R.Belmares, R.C.Bergstrom, Y.Tong, D.R.Corey, M.R.Kanost, and E.J.Goldsmith (2001).
The structure of a Michaelis serpin-protease complex.
  Nat Struct Biol, 8, 979-983.
PDB codes: 1i99 1k9o
  11063688 C.Green, E.Levashina, C.McKimmie, T.Dafforn, J.M.Reichhart, and D.Gubb (2000).
The necrotic gene in Drosophila corresponds to one of a cluster of three serpin transcripts mapping at 43A1.2.
  Genetics, 156, 1117-1127.  
  10933492 P.R.Elliott, X.Y.Pei, T.R.Dafforn, and D.A.Lomas (2000).
Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for rational drug design to prevent conformational disease.
  Protein Sci, 9, 1274-1281.
PDB code: 1qlp
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.