5XN3

Crystal structure of SPSB2 in complex with a rational designed RGD containing cyclic peptide inhibitor of SPSB2-iNOS interaction


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.34 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.181 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Crystal structure of SPSB2 in complex with a rational designed RGD-containing cyclic peptide inhibitor of SPSB2-iNOS interaction.

You, T.Wang, Y.Li, K.Zhang, D.Wei, H.Luo, Y.Li, H.Lu, Y.Su, X.Kuang, Z.

(2017) Biochem Biophys Res Commun 489: 346-352

  • DOI: https://doi.org/10.1016/j.bbrc.2017.05.122
  • Primary Citation of Related Structures:  
    5XN3

  • PubMed Abstract: 

    SPRY domain-containing SOCS box protein 2 (SPSB2) is a negative regulator of inducible nitric oxide synthase (iNOS) that modulates the lifetime of iNOS and thus the levels of nitric oxide (NO) production. Inhibitors that can disrupt the endogenous SPSB2-iNOS interaction and augment NO production have potential as novel antimicrobial and anticancer drugs. In this study, we have designed a cyclic peptide (cR8), containing an RGD motif and the SPSB2 binding motif (DINNNV). ITC and chemical shift perturbation showed that cR8 binds to the iNOS binding site on SPSB2 with a K d of 671 nM, and saturation transfer difference NMR showed that cR8 binds to α v β 3 integrin-expressing cells. Moreover, we determined the crystal structure of SPSB2 in complex with cR8, at a resolution of 1.34 Å. cR8 forms extensive hydrogen bonding with SPSB2 residues, but loss of an intramolecular hydrogen bond that is present in SPSB2-bound iNOS peptide may destabilize the bound conformation of cR8 and lead to a gentle reduction in SPSB2 binding affinity. These results serve as a useful basis for designing site-directed SPSB2 inhibitors in the future.


  • Organizational Affiliation

    Department of Cell Biology and Institute of Biomedicine, Jinan University, Guangzhou 510632, China; Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Guangzhou 510632, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SPRY domain-containing SOCS box protein 2209Homo sapiensMutation(s): 0 
Gene Names: SPSB2GRCC9SSB2
UniProt & NIH Common Fund Data Resources
Find proteins for Q99619 (Homo sapiens)
Explore Q99619 
Go to UniProtKB:  Q99619
PHAROS:  Q99619
GTEx:  ENSG00000111671 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99619
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
cR8 peptide from NOS28Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P35228 (Homo sapiens)
Explore P35228 
Go to UniProtKB:  P35228
PHAROS:  P35228
GTEx:  ENSG00000007171 
Entity Groups  
UniProt GroupP35228
Sequence Annotations
Expand
  • Reference Sequence
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.34 Å
  • R-Value Free: 0.200 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.181 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 32.49α = 90
b = 64.6β = 102.95
c = 47.59γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
iMOSFLMdata reduction
Aimlessdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Natural Science Foundation of ChinaChina31270817
National Natural Science Foundation of ChinaChina81571539

Revision History  (Full details and data files)

  • Version 1.0: 2017-06-14
    Type: Initial release
  • Version 1.1: 2017-07-05
    Changes: Database references
  • Version 1.2: 2023-11-22
    Changes: Data collection, Database references, Derived calculations, Refinement description