1QZQ

human Tyrosyl DNA phosphodiesterase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.185 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Analysis of Human Tyrosyl-DNA Phosphodiesterase I Catalytic Residues.

Raymond, A.C.Rideout, M.C.Staker, B.Hjerrild, K.Burgin Jr., A.B.

(2004) J Mol Biol 338: 895-906

  • DOI: https://doi.org/10.1016/j.jmb.2004.03.013
  • Primary Citation of Related Structures:  
    1QZQ

  • PubMed Abstract: 

    Tyrosyl-DNA phosphodiesterase I (Tdp1) is involved in the repair of DNA lesions created by topoisomerase I in vivo. Tdp1 is a member of the phospholipase D (PLD) superfamily of enzymes and hydrolyzes 3'-phosphotyrosyl bonds to generate 3'-phosphate DNA and free tyrosine in vitro. Here, we use synthetic 3'-(4-nitro)phenyl, 3'-(4-methyl)phenyl, and 3'-tyrosine phosphate oligonucleotides to study human Tdp1. Kinetic analysis of human Tdp1 (hTdp1) shows that the enzyme has nanomolar affinity for all three substrates and the overall in vitro reaction is diffusion-limited. Analysis of active-site mutants using these modified substrates demonstrates that hTdp1 uses an acid/base catalytic mechanism. The results show that histidine 493 serves as the general acid during the initial transesterification, in agreement with hypotheses based on previous crystal structure models. The results also argue that lysine 495 and asparagine 516 participate in the general acid reaction, and the analysis of crystal structures suggests that these residues may function in a proton relay. Together with previous crystal structure data, the new functional data provide a mechanistic understanding of the conserved histidine, lysine and asparagine residues found among all PLD family members.


  • Organizational Affiliation

    Biology Department, San Diego State University, CA 98182-4614, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
tyrosyl-DNA phosphodiesterase 1
A, B
483Homo sapiensMutation(s): 0 
Gene Names: tdp1
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NUW8 (Homo sapiens)
Explore Q9NUW8 
Go to UniProtKB:  Q9NUW8
PHAROS:  Q9NUW8
GTEx:  ENSG00000042088 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NUW8
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.185 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 50.024α = 90
b = 105.131β = 90
c = 194.153γ = 90
Software Package:
Software NamePurpose
CNXrefinement
MAR345data collection
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-05-11
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2018-01-31
    Changes: Experimental preparation
  • Version 1.5: 2024-02-14
    Changes: Data collection, Database references