[English] 日本語
Yorodumi
- PDB-7m2n: Crystal structure of Human Lactate Dehydrogenase A with Inhibitor... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7m2n
TitleCrystal structure of Human Lactate Dehydrogenase A with Inhibitor Compound 15
ComponentsL-lactate dehydrogenase A chain
KeywordsOXIDOREDUCTASE
Function / homology
Function and homology information


L-lactate dehydrogenase / oxidoreductase complex / L-lactate dehydrogenase (NAD+) activity / Pyruvate metabolism / lactate metabolic process / pyruvate metabolic process / substantia nigra development / Regulation of pyruvate metabolism / glycolytic process / cadherin binding ...L-lactate dehydrogenase / oxidoreductase complex / L-lactate dehydrogenase (NAD+) activity / Pyruvate metabolism / lactate metabolic process / pyruvate metabolic process / substantia nigra development / Regulation of pyruvate metabolism / glycolytic process / cadherin binding / mitochondrion / extracellular exosome / identical protein binding / nucleus / membrane / cytosol
Similarity search - Function
L-lactate dehydrogenase / L-lactate dehydrogenase active site. / L-lactate dehydrogenase, active site / L-2-Hydroxyisocaproate Dehydrogenase; Chain A, domain 2 / Lactate dehydrogenase/glycoside hydrolase, family 4, C-terminal / L-lactate/malate dehydrogenase / Lactate/malate dehydrogenase, N-terminal / Lactate/malate dehydrogenase, C-terminal / lactate/malate dehydrogenase, NAD binding domain / lactate/malate dehydrogenase, alpha/beta C-terminal domain ...L-lactate dehydrogenase / L-lactate dehydrogenase active site. / L-lactate dehydrogenase, active site / L-2-Hydroxyisocaproate Dehydrogenase; Chain A, domain 2 / Lactate dehydrogenase/glycoside hydrolase, family 4, C-terminal / L-lactate/malate dehydrogenase / Lactate/malate dehydrogenase, N-terminal / Lactate/malate dehydrogenase, C-terminal / lactate/malate dehydrogenase, NAD binding domain / lactate/malate dehydrogenase, alpha/beta C-terminal domain / Lactate dehydrogenase/glycoside hydrolase, family 4, C-terminal / NAD(P)-binding Rossmann-like Domain / NAD(P)-binding domain superfamily / Alpha-Beta Complex / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE / DI(HYDROXYETHYL)ETHER / Chem-YOJ / L-lactate dehydrogenase A chain
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsGumpena, R. / Ding, J. / Powell, D.A. / Lowther, W.T.
CitationJournal: ACS Medicinal Chemistry Letters / Year: 2021
Title: Dual Glycolate Oxidase/Lactate Dehydrogenase A Inhibitors for Primary Hyperoxaluria
Authors: Ding, J. / Gumpena, R. / Boily, M.O. / Caron, A. / Chong, O. / Cox, J.H. / Dumais, V. / Gaudreault, S. / Graff, A.H. / King, A. / Knight, J. / Oballa, R. / Surendradoss, J. / Tang, T. / Wu, ...Authors: Ding, J. / Gumpena, R. / Boily, M.O. / Caron, A. / Chong, O. / Cox, J.H. / Dumais, V. / Gaudreault, S. / Graff, A.H. / King, A. / Knight, J. / Oballa, R. / Surendradoss, J. / Tang, T. / Wu, J. / Lowther, W.T. / Powell, D.A.
History
DepositionMar 17, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 14, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 18, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: L-lactate dehydrogenase A chain
B: L-lactate dehydrogenase A chain
C: L-lactate dehydrogenase A chain
D: L-lactate dehydrogenase A chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)162,656109
Polymers150,2544
Non-polymers12,402105
Water9,674537
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)83.930, 131.050, 215.518
Angle α, β, γ (deg.)90.00, 99.30, 90.00
Int Tables number5
Space group name H-MI121
Components on special symmetry positions
IDModelComponents
11D-423-

SO4

21D-534-

HOH

Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B
12A
22C
13A
23D
14B
24C
15B
25D
16C
26D

NCS domain segments:

Component-ID: _ / Beg auth comp-ID: ALA / Beg label comp-ID: ALA / End auth comp-ID: PHE / End label comp-ID: PHE / Refine code: _ / Auth seq-ID: 1 - 331 / Label seq-ID: 2 - 332

Dom-IDEns-IDAuth asym-IDLabel asym-ID
11AA
21BB
12AA
22CC
13AA
23DD
14BB
24CC
15BB
25DD
16CC
26DD

NCS ensembles :
ID
1
2
3
4
5
6

-
Components

-
Protein , 1 types, 4 molecules ABCD

#1: Protein
L-lactate dehydrogenase A chain / LDH-A / Cell proliferation-inducing gene 19 protein / LDH muscle subunit / LDH-M / Renal carcinoma ...LDH-A / Cell proliferation-inducing gene 19 protein / LDH muscle subunit / LDH-M / Renal carcinoma antigen NY-REN-59


Mass: 37563.543 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: LDHA, PIG19 / Production host: Escherichia coli (E. coli) / References: UniProt: P00338, L-lactate dehydrogenase

-
Non-polymers , 7 types, 642 molecules

#2: Chemical
ChemComp-NAI / 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE / NADH


Mass: 665.441 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H29N7O14P2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: SO4
#4: Chemical...
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 75 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical
ChemComp-PEG / DI(HYDROXYETHYL)ETHER


Mass: 106.120 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C4H10O3
#7: Chemical
ChemComp-YOJ / 5-[(5'-{1-(4-carboxy-1,3-thiazol-2-yl)-5-(cyclopropylmethyl)-4-[(3-fluoro-4-sulfamoylphenyl)methyl]-1H-pyrazol-3-yl}-2'-fluoro[1,1'-biphenyl]-4-yl)oxy]-1H-1,2,3-triazole-4-carboxylic acid


Mass: 733.721 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C33H25F2N7O7S2 / Feature type: SUBJECT OF INVESTIGATION
#8: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 537 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4.01 Å3/Da / Density % sol: 69.31 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 0.2 M Lithium Sulfate, 0.1 M Sodium Cacodylate pH 6.5, 30% (v/v) PEG 400

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 / Wavelength: 1.54 Å
DetectorType: DECTRIS PILATUS 200K / Detector: PIXEL / Date: Nov 5, 2019
RadiationMonochromator: Cu / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.5→50 Å / Num. obs: 78979 / % possible obs: 100 % / Redundancy: 4.6 % / Rmerge(I) obs: 0.104 / Net I/σ(I): 13.46
Reflection shellResolution: 2.5→2.54 Å / Num. unique obs: 3992 / CC1/2: 0.87

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
HKL-3000data reduction
HKL-3000data scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5W8J

5w8j


Resolution: 2.5→48.89 Å / Cor.coef. Fo:Fc: 0.935 / Cor.coef. Fo:Fc free: 0.9 / SU B: 7.979 / SU ML: 0.179 / Cross valid method: THROUGHOUT / ESU R: 0.341 / ESU R Free: 0.259 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.25769 3910 5 %RANDOM
Rwork0.20938 ---
obs0.21175 74825 97.6 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 37.906 Å2
Baniso -1Baniso -2Baniso -3
1--0 Å20 Å2-0.01 Å2
2---0 Å20 Å2
3---0.01 Å2
Refinement stepCycle: 1 / Resolution: 2.5→48.89 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10170 0 808 537 11515
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.01311174
X-RAY DIFFRACTIONr_bond_other_d0.0010.01710933
X-RAY DIFFRACTIONr_angle_refined_deg1.4611.68115027
X-RAY DIFFRACTIONr_angle_other_deg1.2311.59525154
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.58851319
X-RAY DIFFRACTIONr_dihedral_angle_2_deg39.77823.454443
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.5151903
X-RAY DIFFRACTIONr_dihedral_angle_4_deg25.2071544
X-RAY DIFFRACTIONr_chiral_restr0.0720.21412
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0211968
X-RAY DIFFRACTIONr_gen_planes_other0.0010.022257
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it2.9363.6755280
X-RAY DIFFRACTIONr_mcbond_other2.9353.6755279
X-RAY DIFFRACTIONr_mcangle_it4.3135.5056591
X-RAY DIFFRACTIONr_mcangle_other4.3135.5066592
X-RAY DIFFRACTIONr_scbond_it3.6694.2935894
X-RAY DIFFRACTIONr_scbond_other3.6694.2945895
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other5.5856.1828419
X-RAY DIFFRACTIONr_long_range_B_refined7.55644.07712055
X-RAY DIFFRACTIONr_long_range_B_other7.55944.05512042
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Weight position: 0.05

Ens-IDDom-IDAuth asym-IDNumberRms dev position (Å)
11A101130.06
12B101130.06
21A100380.07
22C100380.07
31A101400.06
32D101400.06
41B101060.06
42C101060.06
51B102110.06
52D102110.06
61C101800.06
62D101800.06
LS refinement shellResolution: 2.5→2.553 Å
RfactorNum. reflection% reflection
Rfree0.313 213 -
Rwork0.258 4086 -
obs--72.14 %

+
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