2O6L

Crystal Structure of the UDP-Glucuronic Acid Binding Domain of the Human Drug Metabolizing UDP-Glucuronosyltransferase 2B7


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.219 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Crystal Structure of the Cofactor-Binding Domain of the Human Phase II Drug-Metabolism Enzyme UDP-Glucuronosyltransferase 2B7.

Miley, M.J.Zielinska, A.K.Keenan, J.E.Bratton, S.M.Radominska-Pandya, A.Redinbo, M.R.

(2007) J Mol Biol 369: 498-511

  • DOI: https://doi.org/10.1016/j.jmb.2007.03.066
  • Primary Citation of Related Structures:  
    2O6L

  • PubMed Abstract: 

    Human UDP-glucuronosyltransferases (UGT) are the dominant phase II conjugative drug metabolism enzymes that also play a central role in processing a range of endobiotic compounds. UGTs catalyze the covalent addition of glucuronic acid sugar moieties to a host of therapeutics and environmental toxins, as well as to a variety of endogenous steroids and other signaling molecules. We report the 1.8-A resolution apo crystal structure of the UDP-glucuronic acid binding domain of human UGT isoform 2B7 (UGT2B7), which catalyzes the conjugative elimination of opioid, antiviral, and anticancer drugs. This is the first crystal structure of any region of a mammalian UGT drug metabolism enzyme. Designated UGT2B7 mutants at residues predicted to interact with the UDP-glucuronic acid cofactor exhibited significantly impaired catalytic activity, with maximum effects observed for amino acids closest to the glucuronic acid sugar transferred to the acceptor molecule. Homology modeling of UGT2B7 with related plant flavonoid glucosyltransferases indicates human UGTs share a common catalytic mechanism. Point mutations at predicted catalytic residues in UGT2B7 abrogated activity, strongly suggesting human UGTs also utilize a serine hydrolase-like catalytic mechanism to facilitate glucuronic acid transfer.


  • Organizational Affiliation

    Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
UDP-glucuronosyltransferase 2B7
A, B
170Homo sapiensMutation(s): 7 
Gene Names: UGT2B7
EC: 2.4.1.17
UniProt & NIH Common Fund Data Resources
Find proteins for P16662 (Homo sapiens)
Explore P16662 
Go to UniProtKB:  P16662
PHAROS:  P16662
GTEx:  ENSG00000171234 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP16662
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A, B
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.219 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 75.175α = 90
b = 75.175β = 90
c = 218.296γ = 120
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
SOLVEphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-05-01
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-27
    Changes: Data collection, Database references, Derived calculations