[English] 日本語
Yorodumi
- PDB-5w8l: Crystal Structure of Lactate Dehydrogenase A in complex with inhi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5w8l
TitleCrystal Structure of Lactate Dehydrogenase A in complex with inhibitor compound 59 and NADH
ComponentsL-lactate dehydrogenase A chain
KeywordsOXIDOREDUCTASE / oxidoreductase inhibitor
Function / homology
Function and homology information


L-lactate dehydrogenase / oxidoreductase complex / Pyruvate metabolism / lactate metabolic process / L-lactate dehydrogenase activity / pyruvate metabolic process / substantia nigra development / Regulation of pyruvate metabolism / glycolytic process / cadherin binding ...L-lactate dehydrogenase / oxidoreductase complex / Pyruvate metabolism / lactate metabolic process / L-lactate dehydrogenase activity / pyruvate metabolic process / substantia nigra development / Regulation of pyruvate metabolism / glycolytic process / cadherin binding / mitochondrion / extracellular exosome / identical protein binding / membrane / nucleus / 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-9YA / 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE / L-lactate dehydrogenase A chain
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.95 Å
AuthorsDavies, D.R. / Dranow, D.M.
CitationJournal: J. Med. Chem. / Year: 2017
Title: Discovery and Optimization of Potent, Cell-Active Pyrazole-Based Inhibitors of Lactate Dehydrogenase (LDH).
Authors: Rai, G. / Brimacombe, K.R. / Mott, B.T. / Urban, D.J. / Hu, X. / Yang, S.M. / Lee, T.D. / Cheff, D.M. / Kouznetsova, J. / Benavides, G.A. / Pohida, K. / Kuenstner, E.J. / Luci, D.K. / ...Authors: Rai, G. / Brimacombe, K.R. / Mott, B.T. / Urban, D.J. / Hu, X. / Yang, S.M. / Lee, T.D. / Cheff, D.M. / Kouznetsova, J. / Benavides, G.A. / Pohida, K. / Kuenstner, E.J. / Luci, D.K. / Lukacs, C.M. / Davies, D.R. / Dranow, D.M. / Zhu, H. / Sulikowski, G. / Moore, W.J. / Stott, G.M. / Flint, A.J. / Hall, M.D. / Darley-Usmar, V.M. / Neckers, L.M. / Dang, C.V. / Waterson, A.G. / Simeonov, A. / Jadhav, A. / Maloney, D.J.
History
DepositionJun 21, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 17, 2018Provider: repository / Type: Initial release
Revision 1.1Mar 13, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.2Apr 3, 2024Group: Refinement description / Category: pdbx_initial_refinement_model

-
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)152,69025
Polymers146,9394
Non-polymers5,75121
Water21,2761181
1
A: L-lactate dehydrogenase A chain
C: L-lactate dehydrogenase A chain
hetero molecules

A: L-lactate dehydrogenase A chain
C: L-lactate dehydrogenase A chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)152,87628
Polymers146,9394
Non-polymers5,93824
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_565-x,-y+1,z1
Buried area28990 Å2
ΔGint-122 kcal/mol
Surface area42120 Å2
MethodPISA
2
D: L-lactate dehydrogenase A chain
hetero molecules

D: L-lactate dehydrogenase A chain
hetero molecules

B: L-lactate dehydrogenase A chain
hetero molecules

B: L-lactate dehydrogenase A chain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)152,50422
Polymers146,9394
Non-polymers5,56518
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_455-x-1,-y,z1
crystal symmetry operation3_445-x-1/2,y-1/2,-z1
crystal symmetry operation4_455x-1/2,-y+1/2,-z1
Buried area27720 Å2
ΔGint-137 kcal/mol
Surface area42020 Å2
MethodPISA
Unit cell
Length a, b, c (Å)135.340, 95.340, 121.720
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212
Components on special symmetry positions
IDModelComponents
11A-727-

HOH

21B-723-

HOH

31B-786-

HOH

-
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: 36734.672 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-NAI / 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE / NADH


Mass: 665.441 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H29N7O14P2
#3: Chemical
ChemComp-9YA / 2-{3-([1,1'-biphenyl]-3-yl)-5-(cyclopropylmethyl)-4-[(4-sulfamoylphenyl)methyl]-1H-pyrazol-1-yl}-1,3-thiazole-4-carboxylic acid


Mass: 570.682 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C30H26N4O4S2
#4: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 13 / Source method: obtained synthetically / Formula: C2H6O2
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1181 / 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: 2.68 Å3/Da / Density % sol: 54.13 %
Crystal growTemperature: 289 K / Method: vapor diffusion / pH: 6
Details: 8% PEG 8000, 100 mM Cacodylate, pH 6.0, 200 mM NaCl

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.97872 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Nov 9, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97872 Å / Relative weight: 1
ReflectionResolution: 1.95→50 Å / Num. obs: 114689 / % possible obs: 99.6 % / Observed criterion σ(I): -3 / Redundancy: 6.26 % / Biso Wilson estimate: 21.47 Å2 / Rmerge(I) obs: 0.122 / Net I/σ(I): 10.06
Reflection shellResolution: 1.95→2 Å / Rmerge(I) obs: 0.505 / Mean I/σ(I) obs: 3.31 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.11.1_2575refinement
PDB_EXTRACT3.22data extraction
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: proprietary structure of the same target

Resolution: 1.95→47.97 Å / SU ML: 0.15 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 16.96
RfactorNum. reflection% reflection
Rfree0.176 2057 1.79 %
Rwork0.147 --
obs-114671 99.6 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 93.72 Å2 / Biso mean: 27.5114 Å2 / Biso min: 11.27 Å2
Refinement stepCycle: final / Resolution: 1.95→47.97 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10114 0 388 1193 11695
Biso mean--25.68 36.27 -
Num. residues----1324
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00610832
X-RAY DIFFRACTIONf_angle_d0.90714750
X-RAY DIFFRACTIONf_chiral_restr0.0541713
X-RAY DIFFRACTIONf_plane_restr0.0051827
X-RAY DIFFRACTIONf_dihedral_angle_d16.8296423
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 15

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.95-1.99530.22761360.185774417577100
1.9953-2.04520.24451260.180874517577100
2.0452-2.10050.20931390.168874187557100
2.1005-2.16240.19851340.158474937627100
2.1624-2.23210.23321450.157774467591100
2.2321-2.31190.17061440.155774787622100
2.3119-2.40450.18611230.14874747597100
2.4045-2.51390.19771300.14975377667100
2.5139-2.64640.19491400.152174657605100
2.6464-2.81220.17761490.147775177666100
2.8122-3.02930.21071390.150375057644100
3.0293-3.33410.14981180.14877515763399
3.3341-3.81640.16561310.13587567769899
3.8164-4.80760.12911690.11987536770599
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)
11.2052-0.04611.09530.0088-0.00671.1816-0.1997-0.5472-0.20510.15060.13660.10370.06230.17330.11320.2947-0.061-0.03510.26140.11590.304119.483939.3661-27.2272
21.002-0.1239-0.59180.1819-0.04540.8567-0.0198-0.0424-0.122-0.0422-0.04710.01430.12750.0240.01680.1841-0.05350.00480.1013-0.00040.172-6.715928.1871-33.3206
30.1661-0.07210.00040.6997-0.31440.55060.0069-0.0175-0.0008-0.0755-0.03920.16050.0418-0.19150.03620.1539-0.0545-0.02980.1764-0.03770.1963-23.69541.3564-40.6113
41.3802-1.68511.22183.9767-2.89343.0872-0.0451-0.14930.01530.16940.02510.0899-0.0169-0.250.04160.1557-0.1181-0.01480.3102-0.04770.2641-34.941133.8675-29.9736
50.27540.2346-0.2162.2055-1.34921.26280.00270.07590.0161-0.67980.04850.2625-0.1452-0.14950.06610.2208-0.0386-0.08870.29610.03870.2424-3.348768.4666-5.4842
60.4471-0.15580.21640.98470.63690.9198-0.0874-0.0683-0.0602-0.01640.0710.124-0.0722-0.1198-0.01070.11760.0085-0.00210.19680.01910.1632-20.214245.8280.2778
70.726-0.22740.2670.3789-0.11860.4861-0.0832-0.1048-0.17610.00490.08520.08610.1603-0.05240.00950.168-0.00450.0420.18020.0390.2079-11.834326.1667.86
81.3146-0.67430.65032.6963-1.1582.1514-0.10720.1961-0.1256-0.1122-0.01150.14160.2258-0.01260.06240.2642-0.08850.0130.15960.03370.3221-21.775917.3689-2.6312
90.340.02690.44060.01470.05960.80750.07430.4203-0.2586-0.294-0.06970.08020.0709-0.2180.04340.45390.011-0.14520.2896-0.05480.2952-20.629251.1994-67.2739
100.894-0.2215-0.43680.30850.37740.70980.04360.0514-0.111-0.2253-0.05950.10140.1028-0.0890.01510.3164-0.0117-0.02760.1207-0.03310.1685-5.012928.1744-61.0392
110.47820.12380.02380.71040.13370.55130.02230.0667-0.0848-0.177-0.0574-0.12520.16370.13870.04480.25240.03820.06290.13350.01650.19216.310329.4083-53.5362
123.07730.77551.87261.31470.90272.4658-0.04070.195-0.2098-0.39450.0282-0.20760.09090.2441-0.04450.45160.12470.11130.2378-0.02620.278921.295517.0348-64.0518
130.08480.03240.09310.43760.4180.9036-0.01950.3513-0.0195-0.4440.0027-0.19290.04880.170.07080.2904-0.12660.12220.495-0.14680.3468-66.0654-21.0823-34.268
140.23130.2246-0.3011.1337-0.64190.8501-0.12360.1953-0.0489-0.10270.0742-0.15820.10230.02460.02590.1658-0.09870.03020.3338-0.03850.1726-47.5551-0.3822-27.989
150.6461-0.1597-0.35270.4073-0.07310.317-0.11660.17870.1591-0.03060.1002-0.0376-0.09560.0210.01840.1673-0.1068-0.03890.27280.04970.1857-53.847820.1553-20.853
161.8941-0.4344-1.08681.53021.09661.7769-0.07750.1641-0.0098-0.12230.03760.0096-0.07-0.0223-0.03490.1983-0.1846-0.04330.34310.07350.2395-42.702128.0587-31.2907
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 1 through 20 )A1 - 20
2X-RAY DIFFRACTION2chain 'A' and (resid 21 through 126 )A21 - 126
3X-RAY DIFFRACTION3chain 'A' and (resid 127 through 308 )A127 - 308
4X-RAY DIFFRACTION4chain 'A' and (resid 309 through 331 )A309 - 331
5X-RAY DIFFRACTION5chain 'B' and (resid 1 through 20 )B1 - 20
6X-RAY DIFFRACTION6chain 'B' and (resid 21 through 126 )B21 - 126
7X-RAY DIFFRACTION7chain 'B' and (resid 127 through 308 )B127 - 308
8X-RAY DIFFRACTION8chain 'B' and (resid 309 through 331 )B309 - 331
9X-RAY DIFFRACTION9chain 'C' and (resid 1 through 20 )C1 - 20
10X-RAY DIFFRACTION10chain 'C' and (resid 21 through 126 )C21 - 126
11X-RAY DIFFRACTION11chain 'C' and (resid 127 through 308 )C127 - 308
12X-RAY DIFFRACTION12chain 'C' and (resid 309 through 331 )C309 - 331
13X-RAY DIFFRACTION13chain 'D' and (resid 1 through 20 )D1 - 20
14X-RAY DIFFRACTION14chain 'D' and (resid 21 through 126 )D21 - 126
15X-RAY DIFFRACTION15chain 'D' and (resid 127 through 308 )D127 - 308
16X-RAY DIFFRACTION16chain 'D' and (resid 309 through 331 )D309 - 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