The high resolution crystal structure of a native thermostable serpin reveals the complex mechanism underpinning the stressed to relaxed transition. (1SNG)

Authors:
Bottomley S.P., Buckle A.M., Butcher R.E., Cabrita L.D., Fulton K.F., Irving J.A., Lesk A.M., Reeve S., Rossjohn J., Smith I., Whisstock J.C.

Abstract:

Serpins fold into a native metastable state and utilize a complex conformational change to inhibit target proteases. An undesirable result of this conformational flexibility is that most inhibitory serpins are heat sensitive, forming inactive polymers at elevated temperatures. However, the prokaryote serpin, thermopin, from Thermobifida fusca is able to function in a heated environment. We have determined the 1.8 A x-ray crystal structure of thermopin in the native, inhibitory conformation. A structural comparison with the previously determined 1.5 A structure of cleaved thermopin provides detailed insight into the complex mechanism of conformational change in serpins. Flexibility in the shutter region and electrostatic interactions at the top of the A beta-sheet (the breach) involving the C-terminal tail, a unique structural feature of thermopin, are postulated to be important for controlling inhibitory activity and triggering conformational change, respectively, in the native state. Here we have discussed the structural basis of how this serpin reconciles the thermodynamic instability necessary for function with the stability required to withstand elevated temperatures.

PDB id(s): 1SNG

Citations:
http://www.ncbi.nlm.nih.gov/pubmed/15590653?dopt=Abstract
http://www.rcsb.org/pdb/explore/explore.do?structureId=1SNG
http://www.ncbi.nlm.nih.gov/pubmed/15590653?dopt=Abstract
http://www.rcsb.org/pdb/explore/explore.do?structureId=1SNG

Persistent Handle: 102.100.100/14

Institution: Monash University

Dataset Information:

  • Datasets: 3
  • Files: 462

Experiment Last Updated: 26th February 2010 15:36

DATASET 1
Dataset Description: APS Source 125 Deg (includes xfiles, denzo)
Dataset Metadata: [Hide]
  • Resolution Limit: 1.76 Å
  • Diffractometer Type: Synchrotron
  • X-Ray Source: CCD - ADSC QUANTUM 4
  • Crystal Name: COG4826: SERINE PROTEASE INHIBITOR
Data Files (281): [Show]
DATASET 2
Dataset Description: APS Source 80 Deg 5 Sec 0.5 Deg - p212121
Dataset Metadata: [Hide]
  • Resolution Limit: 1.76 Å
  • Diffractometer Type: Synchrotron
  • X-Ray Source: CCD - ADSC QUANTUM 4
  • Crystal Name: COG4826: SERINE PROTEASE INHIBITOR
Data Files (179): [Show]
DATASET 3
Dataset Description: Ancillary Files
Data Files (2): [Show]