[English] 日本語
Yorodumi
- PDB-6bb3: Lactate Dehydrogenase in complex with inhibitor 3-((2-chloropheny... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6bb3
TitleLactate Dehydrogenase in complex with inhibitor 3-((2-chlorophenyl)thio)-6-(6-((4-fluorophenyl)amino)pyridin-2-yl)-4-hydroxy-6-(thiophen-3-yl)-5,6-dihydro-2H-pyran-2-one
ComponentsL-lactate dehydrogenase A chain
KeywordsOXIDOREDUCTASE/Inhibitor / inhibitor / OXIDOREDUCTASE / OXIDOREDUCTASE-Inhibitor complex
Function / homology
Function and homology information


sperm fibrous sheath / pyruvate catabolic process / L-lactate dehydrogenase / oxidoreductase complex / pyruvate metabolic process / L-lactate dehydrogenase (NAD+) activity / 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 / pyruvate metabolic process / L-lactate dehydrogenase (NAD+) activity / 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-D4A / NICOTINAMIDE-ADENINE-DINUCLEOTIDE / L-lactate dehydrogenase A chain
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsChen, Z. / Eigenbrot, C.
CitationJournal: To Be Published
Title: Structure-guided optimization and in vivo activities of hydroxylactone and hydroxylactam Inhibitors of Human Lactate Dehydrogenase
Authors: Wei, B.Q. / Labadie, S.S. / Robarge, K. / Chen, J. / Chen, Z. / Corson, L.B. / Ding, C.Z. / DiPasquale, A.G. / Dragovich, P.S. / Eigenbrot, C. / Evangelista, M. / Fauber, B.P. / Gao, Z. / ...Authors: Wei, B.Q. / Labadie, S.S. / Robarge, K. / Chen, J. / Chen, Z. / Corson, L.B. / Ding, C.Z. / DiPasquale, A.G. / Dragovich, P.S. / Eigenbrot, C. / Evangelista, M. / Fauber, B.P. / Gao, Z. / Ge, H. / Hitz, A. / Ho, Q. / Lai, K.W. / Liu, W. / Liu, Y. / Li, C. / Ma, S. / Malek, S. / O'Brien, T. / Pang, J. / Peterson, D. / Salphati, L. / Sideris, S. / Ultsch, M. / Yen, I. / Yue, Q. / Zhang, H. / Zhou, A. / Purkey, H.E.
History
DepositionOct 16, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Oct 24, 2018Provider: repository / Type: Initial release
Revision 1.1Oct 4, 2023Group: Advisory / Data collection ...Advisory / 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 / pdbx_unobs_or_zero_occ_atoms
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
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)151,84019
Polymers146,4144
Non-polymers5,42615
Water2,360131
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area27560 Å2
ΔGint-278 kcal/mol
Surface area43200 Å2
MethodPISA
Unit cell
Length a, b, c (Å)74.700, 80.798, 103.047
Angle α, β, γ (deg.)90.00, 96.77, 90.00
Int Tables number4
Space group name H-MP1211

-
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


Mass: 36603.473 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
#2: Chemical
ChemComp-NAD / NICOTINAMIDE-ADENINE-DINUCLEOTIDE


Mass: 663.425 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H27N7O14P2 / Comment: NAD*YM
#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: SO4
#4: Chemical
ChemComp-D4A / (6R)-3-[(2-chlorophenyl)sulfanyl]-6-{6-[(4-fluorophenyl)amino]pyridin-2-yl}-4-hydroxy-6-(thiophen-3-yl)-5,6-dihydro-2H-pyran-2-one


Mass: 525.014 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C26H18ClFN2O3S2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 131 / 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: 2.11 Å3/Da / Density % sol: 41.68 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7 / Details: PEG3350, sodium malonate

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL17U1 / Wavelength: 0.97915 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Sep 17, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97915 Å / Relative weight: 1
ReflectionResolution: 2.4→50 Å / Num. obs: 47131 / % possible obs: 96.4 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 2.8 % / Biso Wilson estimate: 36 Å2 / Rsym value: 0.086 / Net I/σ(I): 13.5
Reflection shellResolution: 2.4→2.49 Å / Redundancy: 2.9 % / Mean I/σ(I) obs: 2.3 / Num. unique obs: 4834 / Rsym value: 0.597 / % possible all: 99.5

-
Processing

Software
NameVersionClassification
BUSTER2.11.6refinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1I10

1i10


Resolution: 2.4→37.58 Å / Cor.coef. Fo:Fc: 0.918 / Cor.coef. Fo:Fc free: 0.917 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 3.462 / SU Rfree Blow DPI: 0.276
RfactorNum. reflection% reflectionSelection details
Rfree0.224 879 2.15 %RANDOM
Rwork0.208 ---
obs0.209 41271 83.1 %-
Displacement parametersBiso mean: 42.28 Å2
Baniso -1Baniso -2Baniso -3
1-2.4387 Å20 Å2-0.4954 Å2
2---1.8016 Å20 Å2
3----0.6371 Å2
Refine analyzeLuzzati coordinate error obs: 0.31 Å
Refinement stepCycle: 1 / Resolution: 2.4→37.58 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10066 0 351 136 10553
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.00910637HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.114442HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d3706SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes243HARMONIC2
X-RAY DIFFRACTIONt_gen_planes1555HARMONIC5
X-RAY DIFFRACTIONt_it10637HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.72
X-RAY DIFFRACTIONt_other_torsion18.34
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion1385SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact12137SEMIHARMONIC4
LS refinement shellResolution: 2.37→2.43 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.242 -1.79 %
Rwork0.231 1593 -
all0.231 1622 -
obs--44.59 %

+
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