3TK9

Crystal structure of human granzyme H


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.252 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural insights into the substrate specificity of human granzyme H: the functional roles of a novel RKR motif

Wang, L.Zhang, K.Wu, L.Liu, S.Zhang, H.Zhou, Q.Tong, L.Sun, F.Fan, Z.

(2012) J Immunol 188: 765-773

  • DOI: https://doi.org/10.4049/jimmunol.1101381
  • Primary Citation of Related Structures:  
    3TJU, 3TJV, 3TK9

  • PubMed Abstract: 

    Human granzyme H (GzmH) is constitutively expressed in human NK cells that have important roles in innate immune responses against tumors and viruses. GzmH is a chymotrypsin-like serine protease. Its substrate preference and its mechanism of substrate recognition are poorly understood. To provide structural insights into the substrate recognition mechanisms for GzmH, we solved the crystal structures of a D102N-GzmH mutant alone and in complex with a decapeptide substrate and an inhibitor to 2.2 Å, 2.4 Å, and 2.7 Å, respectively. The Thr(189), Gly(216), and Gly(226) specificity triad in the S1 pocket of GzmH defines its preference for bulky, aromatic residues (Tyr and Phe) at the P1 position. Notably, we discovered that an unusual RKR motif (Arg(39)-Lys(40)-Arg(41)), conserved only in GzmH, helps define the S3' and S4' binding regions, indicating the preference for acidic residues at the P3' and P4' sites. Disruption of the RKR motif or the acidic P3' and P4' residues in the substrate abolished the proteolytic activity of GzmH. We designed a tetrapeptide chloromethylketone inhibitor, Ac-PTSY-chloromethylketone, which can selectively and efficiently block the enzymatic and cytotoxic activity of GzmH, providing a useful tool for further studies on the function of GzmH.


  • Organizational Affiliation

    Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Granzyme H226Homo sapiensMutation(s): 1 
Gene Names: GZMHCGL2CTSGL2
EC: 3.4.21
UniProt & NIH Common Fund Data Resources
Find proteins for P20718 (Homo sapiens)
Explore P20718 
Go to UniProtKB:  P20718
PHAROS:  P20718
GTEx:  ENSG00000100450 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP20718
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
B [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.251 
  • R-Value Observed: 0.252 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 63.885α = 90
b = 63.885β = 90
c = 142.464γ = 90
Software Package:
Software NamePurpose
ADSCdata collection
PHASESphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-12-28
    Type: Initial release
  • Version 1.1: 2013-07-03
    Changes: Database references
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description