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PDBsum entry 1xu8

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protein ligands Protein-protein interface(s) links
Signaling protein PDB id
1xu8
Jmol
Contents
Protein chains
365 a.a. *
Ligands
SO4 ×2
Waters ×123
* Residue conservation analysis
PDB id:
1xu8
Name: Signaling protein
Title: The 2.8 a structure of a tumour suppressing serpin
Structure: Maspin. Chain: a, b. Synonym: protease inhibitor 5. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: serpinb5. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
2.80Å     R-factor:   0.224     R-free:   0.286
Authors: J.A.Irving,R.H.Law,K.Ruzyla,T.A.Bashtannyk-Puhalovich,N.Kim, D.M.Worrall,J.Rossjohn,J.C.Whisstock
Key ref:
R.H.Law et al. (2005). The high resolution crystal structure of the human tumor suppressor maspin reveals a novel conformational switch in the G-helix. J Biol Chem, 280, 22356-22364. PubMed id: 15760906 DOI: 10.1074/jbc.M412043200
Date:
25-Oct-04     Release date:   15-Mar-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P36952  (SPB5_HUMAN) -  Serpin B5
Seq:
Struc:
375 a.a.
365 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   4 terms 
  Biological process     cellular component movement   7 terms 
  Biochemical function     protein binding     2 terms  

 

 
DOI no: 10.1074/jbc.M412043200 J Biol Chem 280:22356-22364 (2005)
PubMed id: 15760906  
 
 
The high resolution crystal structure of the human tumor suppressor maspin reveals a novel conformational switch in the G-helix.
R.H.Law, J.A.Irving, A.M.Buckle, K.Ruzyla, M.Buzza, T.A.Bashtannyk-Puhalovich, T.C.Beddoe, K.Nguyen, D.M.Worrall, S.P.Bottomley, P.I.Bird, J.Rossjohn, J.C.Whisstock.
 
  ABSTRACT  
 
Maspin is a serpin that acts as a tumor suppressor in a range of human cancers, including tumors of the breast and lung. Maspin is crucial for development, because homozygous loss of the gene is lethal; however, the precise physiological role of the molecule is unclear. To gain insight into the function of human maspin, we have determined its crystal structure in two similar, but non-isomorphous crystal forms, to 2.1- and 2.8-A resolution, respectively. The structure reveals that maspin adopts the native serpin fold in which the reactive center loop is expelled fully from the A beta-sheet, makes minimal contacts with the core of the molecule, and exhibits a high degree of flexibility. A buried salt bridge unique to maspin orthologues causes an unusual bulge in the region around the D and E alpha-helices, an area of the molecule demonstrated in other serpins to be important for cofactor recognition. Strikingly, the structural data reveal that maspin is able to undergo conformational change in and around the G alpha-helix, switching between an open and a closed form. This change dictates the electrostatic character of a putative cofactor binding surface and highlights this region as a likely determinant of maspin function. The high resolution crystal structure of maspin provides a detailed molecular framework to elucidate the mechanism of function of this important tumor suppressor.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. The x-ray crystal structure of maspin. The A-sheet appears in red, the B-sheet in green, the C-sheet in yellow, the RCL in purple, and the helices (labeled) in gray. Tyrosine residues are in green ball and stick representation and are labeled. Tyr84 (labeled) points into a shallow cavity bounded by the A-, C-, and E-helices. The figure was generated using Molscript (33).
Figure 6.
FIG. 6. Comparisons of maspin structures. A, a structural superposition of the 2.1- and 2.8-Å maspin structures, and the previously determined, non-isomorphous structure of maspin at 3.1 Å (PDB code 1XQG [PDB] (22)) is shown, revealing striking conformational heterogeneity at the G-helix. The C traces are colored as follows: 2.1-Å chain A (red), 2.1-Å chain B (black), 2.8-Å chain A (cyan), 2.8-Å chain B (magenta), 3.1-Å (1XQG) chain A (green). B, superposition of maspin (closed form in red, open form in green) with the native conformations of clade B serpins ovalbumin (black) and PAI-2 (blue).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 22356-22364) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20174634 C.G.Langendorf, T.L.Key, G.Fenalti, W.T.Kan, A.M.Buckle, T.Caradoc-Davies, K.L.Tuck, R.H.Law, and J.C.Whisstock (2010).
The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.
  PLoS One, 5, e9280.
PDB code: 3jz4
20337574 F.Lonardo, X.Li, A.Kaplun, A.Soubani, S.Sethi, S.Gadgeel, and S.Sheng (2010).
The natural tumor suppressor protein maspin and potential application in non small cell lung cancer.
  Curr Pharm Des, 16, 1877-1881.  
19615364 M.Narayan, and S.Twining (2010).
Focus on molecules: maspin.
  Exp Eye Res, 90, 2-3.  
19638634 R.Bass, L.Wagstaff, L.Ravenhill, and V.Ellis (2009).
Binding of extracellular maspin to beta1 integrins inhibits vascular smooth muscle cell migration.
  J Biol Chem, 284, 27712-27720.  
17001697 C.M.Bailey, Z.Khalkhali-Ellis, E.A.Seftor, and M.J.Hendrix (2006).
Biological functions of maspin.
  J Cell Physiol, 209, 617-624.  
16540429 E.I.Chen, and J.R.Yates (2006).
Maspin and tumor metastasis.
  IUBMB Life, 58, 25-29.  
16737556 R.H.Law, Q.Zhang, S.McGowan, A.M.Buckle, G.A.Silverman, W.Wong, C.J.Rosado, C.G.Langendorf, R.N.Pike, P.I.Bird, and J.C.Whisstock (2006).
An overview of the serpin superfamily.
  Genome Biol, 7, 216.  
16176261 J.C.Whisstock, S.P.Bottomley, P.I.Bird, R.N.Pike, and P.Coughlin (2005).
Serpins 2005 - fun between the beta-sheets. Meeting report based upon presentations made at the 4th International Symposium on Serpin Structure, Function and Biology (Cairns, Australia).
  FEBS J, 272, 4868-4873.  
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.