2DQZ

Crystal structure of human carboxylesterase in complex with homatropine, coenzyme A, and palmitate


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.193 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1

Bencharit, S.Edwards, C.C.Morton, C.L.Howard-Williams, E.L.Kuhn, P.Potter, P.M.Redinbo, M.R.

(2006) J Mol Biol 363: 201-214

  • DOI: https://doi.org/10.1016/j.jmb.2006.08.025
  • Primary Citation of Related Structures:  
    2DQY, 2DQZ, 2DR0, 2H7C

  • PubMed Abstract: 

    Human carboxylesterase 1 (hCE1) is a drug and endobiotic-processing serine hydrolase that exhibits relatively broad substrate specificity. It has been implicated in a variety of endogenous cholesterol metabolism pathways including the following apparently disparate reactions: cholesterol ester hydrolysis (CEH), fatty acyl Coenzyme A hydrolysis (FACoAH), acyl-Coenzyme A:cholesterol acyltransfer (ACAT), and fatty acyl ethyl ester synthesis (FAEES). The structural basis for the ability of hCE1 to perform these catalytic actions involving large substrates and products has remained unclear. Here we present four crystal structures of the hCE1 glycoprotein in complexes with the following endogenous substrates or substrate analogues: Coenzyme A, the fatty acid palmitate, and the bile acids cholate and taurocholate. While the active site of hCE1 was known to be promiscuous and capable of interacting with a variety of chemically distinct ligands, these structures reveal that the enzyme contains two additional ligand-binding sites and that each site also exhibits relatively non-specific ligand-binding properties. Using this multisite promiscuity, hCE1 appears structurally capable of assembling several catalytic events depending, apparently, on the physiological state of the cellular environment. These results expand our understanding of enzyme promiscuity and indicate that, in the case of hCE1, multiple non-specific sites are employed to perform distinct catalytic actions.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Liver carboxylesterase 1
A, B, C
542Homo sapiensMutation(s): 0 
EC: 3.1.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P23141 (Homo sapiens)
Explore P23141 
Go to UniProtKB:  P23141
PHAROS:  P23141
GTEx:  ENSG00000198848 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP23141
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 7 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
COA
Query on COA

Download Ideal Coordinates CCD File 
X [auth C]COENZYME A
C21 H36 N7 O16 P3 S
RGJOEKWQDUBAIZ-IBOSZNHHSA-N
SIA
Query on SIA

Download Ideal Coordinates CCD File 
E [auth A],
L [auth B],
T [auth C]
N-acetyl-alpha-neuraminic acid
C11 H19 N O9
SQVRNKJHWKZAKO-YRMXFSIDSA-N
HTQ
Query on HTQ

Download Ideal Coordinates CCD File 
J [auth A],
R [auth B],
Z [auth C]
HOMOTROPINE
C16 H21 N O3
ZTVIKZXZYLEVOL-LXTVHRRPSA-N
PLM
Query on PLM

Download Ideal Coordinates CCD File 
I [auth A],
Q [auth B],
Y [auth C]
PALMITIC ACID
C16 H32 O2
IPCSVZSSVZVIGE-UHFFFAOYSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
D [auth A],
K [auth B],
S [auth C]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
F [auth A]
G [auth A]
M [auth B]
N [auth B]
O [auth B]
F [auth A],
G [auth A],
M [auth B],
N [auth B],
O [auth B],
U [auth C],
V [auth C]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
F
Query on F

Download Ideal Coordinates CCD File 
H [auth A],
P [auth B],
W [auth C]
FLUORIDE ION
F
KRHYYFGTRYWZRS-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.193 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.564α = 90
b = 181.017β = 90
c = 202.56γ = 90
Software Package:
Software NamePurpose
CNSrefinement
ADSCdata collection
MOSFLMdata reduction
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-08-29
    Type: Initial release
  • Version 1.1: 2007-10-22
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Data collection, Database references, Derived calculations, Structure summary
  • Version 1.4: 2023-10-25
    Changes: Data collection, Database references, Refinement description, Structure summary