[English] 日本語
Yorodumi
- PDB-1mx9: Crystal Structure of Human Liver Carboxylesterase in complexed wi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1mx9
TitleCrystal Structure of Human Liver Carboxylesterase in complexed with naloxone methiodide, a heroin analogue
Componentsliver Carboxylesterase I
KeywordsHYDROLASE / esterase / heroin
Function / homology
Function and homology information


cholesterol ester hydrolysis involved in cholesterol transport / methylumbelliferyl-acetate deacetylase / methylumbelliferyl-acetate deacetylase activity / regulation of bile acid secretion / sterol esterase / sterol ester esterase activity / medium-chain fatty acid metabolic process / carboxylesterase / Physiological factors / carboxylesterase activity ...cholesterol ester hydrolysis involved in cholesterol transport / methylumbelliferyl-acetate deacetylase / methylumbelliferyl-acetate deacetylase activity / regulation of bile acid secretion / sterol esterase / sterol ester esterase activity / medium-chain fatty acid metabolic process / carboxylesterase / Physiological factors / carboxylesterase activity / regulation of bile acid biosynthetic process / cellular response to cholesterol / positive regulation of cholesterol metabolic process / reverse cholesterol transport / Phase I - Functionalization of compounds / carboxylic ester hydrolase activity / cholesterol biosynthetic process / Aspirin ADME / negative regulation of cholesterol storage / cellular response to low-density lipoprotein particle stimulus / positive regulation of cholesterol efflux / Metabolism of Angiotensinogen to Angiotensins / cholesterol metabolic process / lipid catabolic process / lipid droplet / epithelial cell differentiation / cholesterol homeostasis / response to toxic substance / endoplasmic reticulum lumen / endoplasmic reticulum / cytoplasm / cytosol
Similarity search - Function
: / Carboxylesterase type B, active site / Carboxylesterases type-B serine active site. / Carboxylesterase type B, conserved site / Carboxylesterases type-B signature 2. / Carboxylesterase, type B / Carboxylesterase family / Alpha/Beta hydrolase fold, catalytic domain / Alpha/Beta hydrolase fold / Rossmann fold ...: / Carboxylesterase type B, active site / Carboxylesterases type-B serine active site. / Carboxylesterase type B, conserved site / Carboxylesterases type-B signature 2. / Carboxylesterase, type B / Carboxylesterase family / Alpha/Beta hydrolase fold, catalytic domain / Alpha/Beta hydrolase fold / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-NLX / Liver carboxylesterase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.9 Å
AuthorsBencharit, S. / Morton, C.L. / Xue, Y. / Potter, P.M. / Redinbo, M.R.
CitationJournal: Nat.Struct.Biol. / Year: 2003
Title: Structural Basis of Heroin and Cocaine Metabolism by a Promiscuous Human Drug-Processing Enzyme
Authors: Bencharit, S. / Morton, C.L. / Xue, Y. / Potter, P.M. / Redinbo, M.R.
History
DepositionOct 1, 2002Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 8, 2003Provider: repository / Type: Initial release
Revision 1.1Apr 28, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Non-polymer description / Version format compliance
Revision 1.3Jul 29, 2020Group: Advisory / Data collection ...Advisory / Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp / entity ...chem_comp / entity / pdbx_chem_comp_identifier / pdbx_entity_nonpoly / pdbx_unobs_or_zero_occ_atoms / struct_ref_seq_dif / struct_site / struct_site_gen
Item: _chem_comp.name / _chem_comp.type ..._chem_comp.name / _chem_comp.type / _entity.pdbx_description / _pdbx_entity_nonpoly.name / _pdbx_unobs_or_zero_occ_atoms.label_asym_id / _struct_ref_seq_dif.details
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 1.4Oct 16, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Remark 300BIOMOLECULE: 1, 2 THIS ENTRY CONTAINS THE CRYSTALLOGRAPHIC ASYMMETRIC UNIT WHICH CONSISTS OF 12 ...BIOMOLECULE: 1, 2 THIS ENTRY CONTAINS THE CRYSTALLOGRAPHIC ASYMMETRIC UNIT WHICH CONSISTS OF 12 CHAIN(S). SEE REMARK 350 FOR INFORMATION ON GENERATING THE BIOLOGICAL MOLECULE(S). The authors have confirmed that human carboxylesterase 1 will form a trimer or hexamer in solution by Atomic Force Microscopy (AFM). They found the ratio of monomer:trimer:hexmer is ~ 10:44:46. 1MX1 contains a hexamer, 1MX5 contains 2 trimers. This entry contains two hexamers. The authors found that the trimer:hexmer ratio is dependent on the type and amount of ligands.
Remark 999SEQUENCE THE AUTHOR'S SEQUENCE HAS NO GLN 362 (CALLED hCEv in: Kroetz DL, McBride OW, Gonzalez FJ. ...SEQUENCE THE AUTHOR'S SEQUENCE HAS NO GLN 362 (CALLED hCEv in: Kroetz DL, McBride OW, Gonzalez FJ.Glycosylation-dependent activity of baculovirus-expressed human liver carboxylesterases: cDNA cloning and characterization of two highly similar enzyme forms. Biochemistry 1993 Nov 2;32(43):11606-17)

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: liver Carboxylesterase I
B: liver Carboxylesterase I
C: liver Carboxylesterase I
D: liver Carboxylesterase I
E: liver Carboxylesterase I
F: liver Carboxylesterase I
G: liver Carboxylesterase I
H: liver Carboxylesterase I
I: liver Carboxylesterase I
J: liver Carboxylesterase I
K: liver Carboxylesterase I
L: liver Carboxylesterase I
hetero molecules


Theoretical massNumber of molelcules
Total (without water)733,12137
Polymers726,13612
Non-polymers6,98525
Water20,3391129
1
A: liver Carboxylesterase I
B: liver Carboxylesterase I
C: liver Carboxylesterase I
D: liver Carboxylesterase I
E: liver Carboxylesterase I
F: liver Carboxylesterase I
hetero molecules


Theoretical massNumber of molelcules
Total (without water)366,67119
Polymers363,0686
Non-polymers3,60313
Water1086
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area22680 Å2
ΔGint-49 kcal/mol
Surface area106990 Å2
MethodPISA
2
G: liver Carboxylesterase I
H: liver Carboxylesterase I
I: liver Carboxylesterase I
J: liver Carboxylesterase I
K: liver Carboxylesterase I
L: liver Carboxylesterase I
hetero molecules


Theoretical massNumber of molelcules
Total (without water)366,45018
Polymers363,0686
Non-polymers3,38212
Water1086
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area22490 Å2
ΔGint-46 kcal/mol
Surface area105970 Å2
MethodPISA
Unit cell
Length a, b, c (Å)91.174, 120.711, 177.017
Angle α, β, γ (deg.)90.28, 89.32, 99.22
Int Tables number1
Space group name H-MP1
DetailsThe biological assembly is two hexamers formed by four trimers in one asymmetric unit.

-
Components

#1: Protein
liver Carboxylesterase I / hCEv / Acyl coenzyme A:cholesterol acyltransferase / ACAT / Monocyte/macrophage serine esterase / ...hCEv / Acyl coenzyme A:cholesterol acyltransferase / ACAT / Monocyte/macrophage serine esterase / HMSE / Serine esterase 1


Mass: 60511.328 Da / Num. of mol.: 12
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): SF21 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P23141, carboxylesterase
#2: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 13
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#3: Chemical
ChemComp-NLX / (5A,17R)-4,5-EPOXY-3,14-DIHYDROXY-17-METHYL-6-OXO-17-(2-PROPENYL)-MORPHINANIUM / N-METHYLNALOXONIUM


Mass: 342.409 Da / Num. of mol.: 12 / Source method: obtained synthetically / Formula: C20H24NO4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1129 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.65 Å3/Da / Density % sol: 53.52 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / pH: 5.5
Details: PEG3350, Glycerol, lithium sulfate, lithium chloride, sodium chloride, sodium citrate, pH 5.5, VAPOR DIFFUSION, SITTING DROP, temperature 298.0K
Crystal grow
*PLUS
Temperature: 22 ℃ / pH: 7.4
Components of the solutions
*PLUS
IDConc.Common nameCrystal-IDSol-IDDetailsChemical formula
13 mg/mlprotein1drop
250 mMHEPES1droppH7.4
310 mMnaloxone methiodide1dropor 100mM homatropine
410 %(w/v)PEG33501reservoir
50.4 M1reservoirLi2SO4
60.1 M1reservoirNaCl
70.1 M1reservoirLiCl
80.1 Mcitrate1reservoirpH5.5
95 %glycerol1reservoir

-
Data collection

DiffractionMean temperature: 200 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1.5418 Å
DetectorType: MARRESEARCH / Detector: CCD / Date: Jul 15, 2002
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.9→50 Å / Num. all: 158131 / Num. obs: 157959 / % possible obs: 96.3 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Biso Wilson estimate: 36.5 Å2
Reflection shellResolution: 2.9→3 Å / % possible all: 95.7
Reflection
*PLUS
Lowest resolution: 30 Å / Redundancy: 1.8 % / Num. measured all: 285255 / Rmerge(I) obs: 0.092
Reflection shell
*PLUS
Highest resolution: 2.9 Å / Lowest resolution: 3.08 Å / % possible obs: 95.7 % / Rmerge(I) obs: 0.246 / Mean I/σ(I) obs: 2.4

-
Processing

Software
NameVersionClassification
HKL-2000data collection
SCALEPACKdata scaling
AMoREphasing
CNS1refinement
HKL-2000data reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.9→29.82 Å / Rfactor Rfree error: 0.003 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 2
RfactorNum. reflection% reflectionSelection details
Rfree0.28 11073 7 %RANDOM
Rwork0.214 ---
all0.247 164970 --
obs0.214 157959 95.7 %-
Solvent computationSolvent model: FLAT MODEL / Bsol: 31.7312 Å2 / ksol: 0.31259 e/Å3
Displacement parametersBiso mean: 44 Å2
Baniso -1Baniso -2Baniso -3
1-8.97 Å23.92 Å21.08 Å2
2---1.72 Å20.55 Å2
3----7.24 Å2
Refine analyzeLuzzati coordinate error free: 0.49 Å / Luzzati sigma a free: 0.55 Å
Refinement stepCycle: LAST / Resolution: 2.9→29.82 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms49523 0 482 1129 51134
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.008
X-RAY DIFFRACTIONc_angle_deg1.4
X-RAY DIFFRACTIONc_dihedral_angle_d23
X-RAY DIFFRACTIONc_improper_angle_d0.89
X-RAY DIFFRACTIONc_mcbond_it1.331.5
X-RAY DIFFRACTIONc_mcangle_it2.322
X-RAY DIFFRACTIONc_scbond_it1.82
X-RAY DIFFRACTIONc_scangle_it2.822.5
LS refinement shellResolution: 2.9→3.08 Å / Rfactor Rfree error: 0.009 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.374 1762 6.9 %
Rwork0.3 23785 -
obs--92.9 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1PROTEIN_REP.PARAMPROTEIN_NOHYDROGEN.TOP
X-RAY DIFFRACTION2CARBOHYDRATE.PARAMCARBOHYDRATE.TOP
X-RAY DIFFRACTION3WATER_REP.PARAMWATER.TOP
X-RAY DIFFRACTION4ION.PARAMION.TOP
X-RAY DIFFRACTION5NLX.PARNLX.TOP
Refinement
*PLUS
Highest resolution: 2.9 Å / Lowest resolution: 30 Å / % reflection Rfree: 7 % / Rfactor Rfree: 0.28
Solvent computation
*PLUS
Displacement parameters
*PLUS
Refine LS restraints
*PLUS
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_dihedral_angle_d
X-RAY DIFFRACTIONc_dihedral_angle_deg23
X-RAY DIFFRACTIONc_improper_angle_d
X-RAY DIFFRACTIONc_improper_angle_deg0.89
LS refinement shell
*PLUS
Highest resolution: 2.9 Å / Rfactor Rfree: 0.418 / Rfactor Rwork: 0.339

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more