[English] 日本語
Yorodumi
- PDB-4ajp: Human LDHA in complex with 2-((4-(4-((3-((2-methyl-1,3-benzothiaz... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4ajp
TitleHuman LDHA in complex with 2-((4-(4-((3-((2-methyl-1,3-benzothiazol- 6yl)amino)-3-oxo-propyl)amino)-4-oxo-butyl)phenyl)methyl)propanedioic acid
ComponentsL-LACTATE DEHYDROGENASE A CHAIN
KeywordsOXIDOREDUCTASE/INHIBITOR / OXIDOREDUCTASE-INHIBITOR COMPLEX / FRAGMENT BASED LEAD GENERATED INHIBITORS
Function / homology
Function and homology information


sperm fibrous sheath / pyruvate catabolic process / L-lactate dehydrogenase / oxidoreductase complex / L-lactate dehydrogenase (NAD+) activity / pyruvate metabolic process / Pyruvate metabolism / lactate metabolic process / glucose catabolic process to lactate via pyruvate / substantia nigra development ...sperm fibrous sheath / pyruvate catabolic process / L-lactate dehydrogenase / oxidoreductase complex / L-lactate dehydrogenase (NAD+) activity / pyruvate metabolic process / Pyruvate metabolism / lactate metabolic process / glucose catabolic process to lactate via pyruvate / 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
Chem-88N / L-lactate dehydrogenase A chain
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.38 Å
AuthorsTucker, J.A. / Brassington, C. / Caputo, A. / Ward, R. / Pearson, S. / Watson, M. / Tart, J. / Davies, G.
CitationJournal: J.Med.Chem. / Year: 2012
Title: The Design and Synthesis of Novel Lactate Dehydrogenase a Inhibitors by Fragment-Based Lead Generation
Authors: Ward, R. / Brassington, C. / Breeze, A.L. / Caputo, A. / Critchlow, S. / Davies, G. / Goodwin, L. / Hassall, G. / Greenwood, R. / Holdgate, G. / Mrosek, M. / Norman, R.A. / Pearson, S. / ...Authors: Ward, R. / Brassington, C. / Breeze, A.L. / Caputo, A. / Critchlow, S. / Davies, G. / Goodwin, L. / Hassall, G. / Greenwood, R. / Holdgate, G. / Mrosek, M. / Norman, R.A. / Pearson, S. / Tart, J. / Tucker, J.A. / Vogtherr, M. / Whittaker, D. / Wingfield, J. / Winter, J. / Hudson, K.
History
DepositionFeb 16, 2012Deposition site: PDBE / Processing site: PDBE
Revision 1.0Mar 21, 2012Provider: repository / Type: Initial release
Revision 1.1Apr 25, 2012Group: Other
Revision 1.2Sep 17, 2014Group: Atomic model / Derived calculations / Non-polymer description
Revision 1.3Dec 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / diffrn_detector / pdbx_database_status / pdbx_initial_refinement_model / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _diffrn_detector.type / _pdbx_database_status.status_code_sf / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_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)153,05322
Polymers149,7294
Non-polymers3,32318
Water7,098394
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area23990 Å2
ΔGint-297.4 kcal/mol
Surface area40070 Å2
MethodPISA
Unit cell
Length a, b, c (Å)63.980, 136.780, 83.790
Angle α, β, γ (deg.)90.00, 102.31, 90.00
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS oper:
IDCodeMatrixVector
1given(-0.99982, -0.01906, 3.0E-5), (-0.01841, 0.96616, 0.25727), (-0.00494, 0.25722, -0.96634)-13.77443, -5.81798, 43.32919
2given(-0.91798, 0.0576, -0.39241), (0.04428, -0.96833, -0.24573), (-0.39414, -0.24295, 0.88636)-4.38953, -27.74323, -4.5601
3given(0.91948, -0.03211, 0.39182), (-0.03161, -0.99947, -0.00772), (0.39186, -0.00529, -0.92001)-8.75757, -33.51753, 40.79667

-
Components

#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 / LACTATE DEHYDROGENASE A


Mass: 37432.344 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Tissue: MUSCLE / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / Variant (production host): STAR / References: UniProt: P00338, L-lactate dehydrogenase
#2: Chemical
ChemComp-88N / {4-[4-({3-[(2-METHYL-1,3-BENZOTHIAZOL-6-YL)AMINO]-3-OXOPROPYL}AMINO)-4-OXOBUTYL]BENZYL}PROPANEDIOIC ACID


Mass: 497.563 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C25H27N3O6S
#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 11 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 394 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.32 Å3/Da / Density % sol: 47 % / Description: NONE
Crystal growpH: 6.5
Details: 1.6M AMMONIUM SULPHATE, 0.1M MES PH 6.5, 10% 1, 4-DIOXANE

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID29 / Wavelength: 0.97627
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 15, 2010 / Details: MIRRORS
RadiationMonochromator: SI(311) OR SI(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97627 Å / Relative weight: 1
ReflectionResolution: 2.31→56.9 Å / Num. obs: 59591 / % possible obs: 97 % / Observed criterion σ(I): 2 / Redundancy: 3.3 % / Rmerge(I) obs: 0.12 / Net I/σ(I): 8.1
Reflection shellResolution: 2.31→2.4 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.54 / Mean I/σ(I) obs: 2.3 / % possible all: 88.7

-
Processing

Software
NameVersionClassification
REFMAC5.6.0117refinement
XDSdata reduction
SCALAdata scaling
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1I10

1i10


Resolution: 2.38→56.85 Å / Cor.coef. Fo:Fc: 0.951 / Cor.coef. Fo:Fc free: 0.921 / SU B: 13.167 / SU ML: 0.16 / Cross valid method: THROUGHOUT / ESU R: 0.415 / ESU R Free: 0.235 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. DISORDERED SIDE-CHAINS HAVE BEEN TRUNCATED. U VALUES WITH TLS ADDED.
RfactorNum. reflection% reflectionSelection details
Rfree0.21467 2806 5 %RANDOM
Rwork0.16563 ---
obs0.16808 52964 98.83 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 37.731 Å2
Baniso -1Baniso -2Baniso -3
1-4.29 Å20 Å21.22 Å2
2---2.19 Å20 Å2
3----1.58 Å2
Refinement stepCycle: LAST / Resolution: 2.38→56.85 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10057 0 213 394 10664
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.01910500
X-RAY DIFFRACTIONr_bond_other_d0.0010.026925
X-RAY DIFFRACTIONr_angle_refined_deg1.3661.96714249
X-RAY DIFFRACTIONr_angle_other_deg0.913317059
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.35851324
X-RAY DIFFRACTIONr_dihedral_angle_2_deg40.79124.949392
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.892151836
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.4771544
X-RAY DIFFRACTIONr_chiral_restr0.0750.21670
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0211614
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021970
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_it
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.38→2.442 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.266 199 -
Rwork0.196 3829 -
obs--98.87 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.09210.1921-0.07620.6558-0.07330.5329-0.0247-0.0179-0.0044-0.0786-0.0065-0.0977-0.01990.02810.03120.01440.0063-0.00560.09770.00580.11175.6453-0.278311.1742
20.1279-0.0423-0.16240.5588-0.0470.48030.00890.00990.01810.09480.00670.0896-0.0554-0.0725-0.01560.02480.013-0.00030.0901-0.01670.087-19.2658-3.383132.3727
30.04880.11340.04280.75850.08190.4284-0.03210.0016-0.0223-0.14460.00670.03530.0345-0.0490.02540.0464-0.0038-0.00730.0717-0.02060.0686-13.9213-29.94743.286
40.028-0.0769-0.02880.6251-0.17240.3771-0.0189-0.0002-0.02270.0857-0.0327-0.08340.0490.03350.05150.0291-0.0005-0.01490.08160.00480.08830.6515-33.323832.6116
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A1 - 331
2X-RAY DIFFRACTION2B1 - 331
3X-RAY DIFFRACTION3C1 - 331
4X-RAY DIFFRACTION4D1 - 331

+
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