5AHO

Crystal structure of human 5' exonuclease Apollo


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.16 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.207 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

The Structures of the Snm1A and Snm1B/Apollo Nuclease Domains Reveal a Potential Basis for Their Distinct DNA Processing Activities.

Allerston, C.K.Lee, S.Y.Newman, J.A.Schofield, C.J.Mchugh, P.J.Gileadi, O.

(2015) Nucleic Acids Res 43: 11047

  • DOI: https://doi.org/10.1093/nar/gkv1256
  • Primary Citation of Related Structures:  
    5AHO, 5AHR

  • PubMed Abstract: 

    The human SNM1A and SNM1B/Apollo proteins are members of an extended family of eukaryotic nuclease containing a motif related to the prokaryotic metallo-β-lactamase (MBL) fold. SNM1A is a key exonuclease during replication-dependent and transcription-coupled interstrand crosslink repair, while SNM1B/Apollo is required for maintaining telomeric overhangs. Here, we report the crystal structures of SNM1A and SNM1B at 2.16 Å. While both proteins contain a typical MBL-β-CASP domain, a region of positive charge surrounds the active site of SNM1A, which is absent in SNM1B and explains the greater apparent processivity of SNM1A. The structures of both proteins also reveal a putative, wide DNA-binding groove. Extensive mutagenesis of this groove, coupled with detailed biochemical analysis, identified residues that did not impact on SNM1A catalytic activity, but drastically reduced its processivity. Moreover, we identified a key role for this groove for efficient digestion past DNA interstrand crosslinks, facilitating the key DNA repair reaction catalysed by SNM1A. Together, the architecture and dimensions of this groove, coupled to the surrounding region of high positive charge, explain the remarkable ability of SNM1A to accommodate and efficiently digest highly distorted DNA substrates, such as those containing DNA lesions.


  • Organizational Affiliation

    Structural Genomics Consortium, Old Road Campus Research Building, Roosevelt Drive, University of Oxford, Oxford OX3 7DQ, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
5' EXONUCLEASE APOLLO336Homo sapiensMutation(s): 0 
EC: 3.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q9H816 (Homo sapiens)
Explore Q9H816 
Go to UniProtKB:  Q9H816
PHAROS:  Q9H816
GTEx:  ENSG00000118655 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9H816
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TLA
Query on TLA

Download Ideal Coordinates CCD File 
G [auth A],
J [auth A]
L(+)-TARTARIC ACID
C4 H6 O6
FEWJPZIEWOKRBE-JCYAYHJZSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
H [auth A],
I [auth A]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
B [auth A]
C [auth A]
D [auth A]
E [auth A]
F [auth A]
B [auth A],
C [auth A],
D [auth A],
E [auth A],
F [auth A],
K [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.16 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.207 
  • Space Group: P 41 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 143.092α = 90
b = 143.092β = 90
c = 143.092γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-02-18
    Type: Initial release
  • Version 1.1: 2016-02-24
    Changes: Database references
  • Version 1.2: 2018-01-24
    Changes: Structure summary