4N6O

Crystal structure of reduced legumain in complex with cystatin E/M


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


This is version 3.0 of the entry. See complete history


Literature

Structure and mechanism of an aspartimide-dependent Peptide ligase in human legumain.

Dall, E.Fegg, J.C.Briza, P.Brandstetter, H.

(2015) Angew Chem Int Ed Engl 54: 2917-2921

  • DOI: https://doi.org/10.1002/anie.201409135
  • Primary Citation of Related Structures:  
    4N6L, 4N6M, 4N6N, 4N6O

  • PubMed Abstract: 

    Peptide ligases expand the repertoire of genetically encoded protein architectures by synthesizing new peptide bonds, energetically driven by ATP or NTPs. Here, we report the discovery of a genuine ligase activity in human legumain (AEP) which has important roles in immunity and tumor progression that were believed to be due to its established cysteine protease activity. Defying dogma, the ligase reaction is independent of the catalytic cysteine but exploits an endogenous energy reservoir that results from the conversion of a conserved aspartate to a metastable aspartimide. Legumain's dual protease-ligase activities are pH- and thus localization controlled, dominating at acidic and neutral pH, respectively. Their relevance includes reversible on-off switching of cystatin inhibitors and enzyme (in)activation, and may affect the generation of three-dimensional MHC epitopes. The aspartate-aspartimide (succinimide) pair represents a new paradigm of coupling endergonic reactions in ATP-scarce environments.


  • Organizational Affiliation

    Department of Molecular Biology, University of Salzburg, 5020 Salzburg (Austria).


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
legumain278Homo sapiensMutation(s): 1 
Gene Names: LGMNPRSC1
EC: 3.4.22.34
UniProt & NIH Common Fund Data Resources
Find proteins for Q99538 (Homo sapiens)
Explore Q99538 
Go to UniProtKB:  Q99538
PHAROS:  Q99538
GTEx:  ENSG00000100600 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99538
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
cystatin-M131Homo sapiensMutation(s): 0 
Gene Names: CST6
UniProt & NIH Common Fund Data Resources
Find proteins for Q15828 (Homo sapiens)
Explore Q15828 
Go to UniProtKB:  Q15828
PHAROS:  Q15828
GTEx:  ENSG00000175315 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15828
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

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Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
D
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.209 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.58α = 90
b = 85.55β = 94.61
c = 58.92γ = 90
Software Package:
Software NamePurpose
MxCuBEdata collection
PHASERphasing
REFMACrefinement
iMOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-02-11
    Type: Initial release
  • Version 1.1: 2015-03-11
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Database references, Derived calculations, Structure summary
  • Version 2.1: 2023-09-20
    Changes: Data collection, Database references, Refinement description, Structure summary
  • Version 3.0: 2023-11-15
    Changes: Atomic model, Data collection, Derived calculations