[English] 日本語
Yorodumi
- PDB-4qo8: Lactate Dehydrogenase A in complex with substituted 3-Hydroxy-2-m... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4qo8
TitleLactate Dehydrogenase A in complex with substituted 3-Hydroxy-2-mercaptocyclohex-2-enone compound 104
ComponentsL-lactate dehydrogenase A chain
Keywordsoxidoreductase/oxidoreductase inhibitor / oxidoreductase / Nicotinamide adenine dinucleotide / oxidoreductase-oxidoreductase inhibitor complex
Function / homology
Function and homology information


oxidoreductase complex / lactate metabolic process / Pyruvate metabolism / L-lactate dehydrogenase / L-lactate dehydrogenase activity / pyruvate metabolic process / substantia nigra development / glycolytic process / cadherin binding / mitochondrion ...oxidoreductase complex / lactate metabolic process / Pyruvate metabolism / L-lactate dehydrogenase / L-lactate dehydrogenase activity / pyruvate metabolic process / substantia nigra development / glycolytic process / cadherin binding / mitochondrion / extracellular exosome / membrane / identical protein binding / nucleus / cytosol
Similarity search - Function
L-lactate dehydrogenase active site. / L-lactate dehydrogenase / 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 active site. / L-lactate dehydrogenase / 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-36U / LACTIC ACID / 1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE / L-lactate dehydrogenase A chain
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.001 Å
AuthorsEigenbrot, C. / Ultsch, M.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2014
Title: Identification of substituted 3-hydroxy-2-mercaptocyclohex-2-enones as potent inhibitors of human lactate dehydrogenase.
Authors: Dragovich, P.S. / Fauber, B.P. / Boggs, J. / Chen, J. / Corson, L.B. / Ding, C.Z. / Eigenbrot, C. / Ge, H. / Giannetti, A.M. / Hunsaker, T. / Labadie, S. / Li, C. / Liu, Y. / Liu, Y. / Ma, S. ...Authors: Dragovich, P.S. / Fauber, B.P. / Boggs, J. / Chen, J. / Corson, L.B. / Ding, C.Z. / Eigenbrot, C. / Ge, H. / Giannetti, A.M. / Hunsaker, T. / Labadie, S. / Li, C. / Liu, Y. / Liu, Y. / Ma, S. / Malek, S. / Peterson, D. / Pitts, K.E. / Purkey, H.E. / Robarge, K. / Salphati, L. / Sideris, S. / Ultsch, M. / VanderPorten, E. / Wang, J. / Wei, B. / Xu, Q. / Yen, I. / Yue, Q. / Zhang, H. / Zhang, X. / Zhou, A.
History
DepositionJun 19, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 16, 2014Provider: repository / Type: Initial release
Revision 1.1Aug 13, 2014Group: Database references
Revision 1.2Sep 3, 2014Group: Database references
Revision 1.3Sep 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / 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 / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 2.0Nov 15, 2023Group: Atomic model / Data collection
Category: atom_site / atom_site_anisotrop ...atom_site / atom_site_anisotrop / chem_comp_atom / chem_comp_bond
Item: _atom_site.auth_atom_id / _atom_site.label_atom_id ..._atom_site.auth_atom_id / _atom_site.label_atom_id / _atom_site_anisotrop.pdbx_auth_atom_id / _atom_site_anisotrop.pdbx_label_atom_id / _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_1 / _chem_comp_bond.atom_id_2

-
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)151,46419
Polymers146,4144
Non-polymers5,05015
Water13,926773
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area27740 Å2
ΔGint-232 kcal/mol
Surface area43620 Å2
MethodPISA
Unit cell
Length a, b, c (Å)168.352, 81.257, 120.760
Angle α, β, γ (deg.)90.00, 117.61, 90.00
Int Tables number5
Space group name H-MC121

-
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: 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

-
Non-polymers , 6 types, 788 molecules

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


Mass: 665.441 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C21H29N7O14P2
#3: Chemical ChemComp-EPE / 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID / HEPES / HEPES


Mass: 238.305 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C8H18N2O4S / Comment: pH buffer*YM
#4: Chemical
ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: SO4
#5: Chemical ChemComp-36U / (5S)-2-[(2-chlorophenyl)sulfanyl]-5-(2,6-dichlorophenyl)-3-hydroxycyclohex-2-en-1-one


Mass: 399.719 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C18H13Cl3O2S
#6: Chemical ChemComp-LAC / LACTIC ACID / Lactic acid


Mass: 90.078 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H6O3
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 773 / 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: 2.5 Å3/Da / Density % sol: 50.79 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7
Details: PEG3350, sodium malonate, pH 7.0, VAPOR DIFFUSION, SITTING DROP, temperature 293K

-
Data collection

DiffractionMean temperature: 110 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 0.9774 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 26, 2011
RadiationMonochromator: Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9774 Å / Relative weight: 1
ReflectionResolution: 2→50 Å / Num. all: 97169 / Num. obs: 97141 / % possible obs: 100 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 3.6 % / Biso Wilson estimate: 29 Å2 / Rsym value: 0.075 / Net I/σ(I): 14.8

-
Processing

Software
NameVersionClassification
BOSdata collection
PHASERphasing
PHENIX(phenix.refine: 1.8.2_1309)refinement
HKL-2000data reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4M49

4m49


Resolution: 2.001→42.415 Å / SU ML: 0.18 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 25.35 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2044 586 0.6 %random
Rwork0.1565 ---
all0.16 97169 --
obs0.1568 97141 99.6 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refine analyzeLuzzati coordinate error obs: 0.18 Å
Refinement stepCycle: LAST / Resolution: 2.001→42.415 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms10272 0 319 773 11364
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00610997
X-RAY DIFFRACTIONf_angle_d1.00314960
X-RAY DIFFRACTIONf_dihedral_angle_d18.1024378
X-RAY DIFFRACTIONf_chiral_restr0.0681729
X-RAY DIFFRACTIONf_plane_restr0.0041847
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.0006-2.20190.23211550.18223779X-RAY DIFFRACTION99
2.2019-2.52050.25541410.165724150X-RAY DIFFRACTION100
2.5205-3.17540.21191320.179724183X-RAY DIFFRACTION100
3.1754-42.42490.1841580.139624443X-RAY DIFFRACTION100
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)
10.287-0.0055-0.6280.10660.25191.85270.0461-0.26660.2946-0.16740.0702-0.3462-0.26750.3577-0.10230.3248-0.03830.00390.403-0.0060.311949.4023-2.97057.4271
20.6536-0.4461-0.11311.83930.43521.0529-0.0597-0.01120.05930.0827-0.0193-0.1399-0.17750.08130.0810.2878-0.0355-0.02510.19960.02370.226747.42816.930329.8909
35.08090.2559-0.10355.36581.50926.7482-0.2574-1.20590.27230.95080.0661-0.28960.30320.59150.12510.5258-0.0189-0.08290.4992-0.04940.376852.381722.873340.0893
41.10640.2659-0.40180.286-0.35451.2641-0.0021-0.14780.11730.24470.0038-0.0324-0.3041-0.0288-0.0130.52590.03610.01430.2221-0.01790.306630.838720.336740.5694
51.2568-0.38060.57270.74970.4741.0722-0.1053-0.26370.08380.34730.09650.0412-0.1917-0.14210.01880.48080.03550.02310.2412-0.00430.281829.672216.214645.1722
61.9410.41351.05511.86680.83822.4441-0.1064-0.02920.46640.26490.02650.032-0.60440.08430.08130.60510.0016-0.02380.21670.00770.347933.488332.560339.2325
73.3368-2.2377-1.67881.55511.11110.8692-0.1532-0.1777-0.28240.88080.09540.220.1069-0.2290.03080.52670.0110.0910.45140.03940.296610.63651.850250.2785
81.4881-1.06730.4641.706-0.28430.6635-0.1531-0.24940.05980.40210.14080.0146-0.0719-0.19630.00420.38220.03280.0390.25120.00060.198234.0389-4.374246.894
92.1685-0.58470.41461.57280.09721.4762-0.0182-0.1647-0.10230.3710.0493-0.0714-0.1368-0.0453-0.05190.31490.0064-0.02950.16260.0140.159547.3185-16.193550.7621
100.4989-0.23510.12730.958-0.18272.44620.00010.0772-0.05990.0619-0.0064-0.05890.10960.14340.00740.1938-0.0112-0.01620.1935-0.00690.200146.9136-19.020228.6352
110.52990.2320.80192.06412.69055.1905-0.02460.09370.12460.02340.2159-0.4537-0.03330.39-0.20550.2363-0.0114-0.04810.29480.0220.336558.2694-10.863830.6458
121.623-0.22990.47341.68410.47931.6884-0.0220.0287-0.30160.12620.0965-0.0130.22440.0875-0.07460.2798-0.01570.03060.20070.0020.219743.1695-24.271734.4548
132.4693-3.3575-0.18044.60980.20750.0097-0.5628-0.0497-0.84760.50540.19170.99590.4689-0.21130.44830.5516-0.1519-0.01580.34470.040.486527.552-29.53229.24
141.315-0.5184-0.38350.7440.21791.27690.0478-0.0256-0.1639-0.01460.01390.11720.0163-0.225-0.070.2223-0.02860.00780.31790.02680.306911.7456-12.294922.2186
156.7615-3.87353.92514.6106-1.6163.0892-0.0520.12150.0878-0.4372-0.18830.5411-0.0147-0.43640.19530.30570.0139-0.02010.6256-0.02420.4695-7.3778-7.512923.9243
160.88370.25540.35841.17290.09371.0589-0.0208-0.02140.08350.1380.01860.3615-0.261-0.4094-0.0040.26450.08460.0730.38950.01360.29945.07359.508631.6043
171.49011.79240.92167.01172.20392.18870.0472-0.20810.29990.0351-0.42641.3518-0.1073-0.62720.32160.36550.15590.1250.717-0.00320.6154-11.29918.2235.1352
180.09770.69960.07795.00570.84530.15820.43930.39060.3204-0.7165-0.0948-0.0505-0.6984-0.1496-0.3930.65150.0744-0.06330.41240.09740.399225.389427.627622.1414
191.0551-0.3177-0.79411.4810.17742.03810.02770.08150.03740.01030.0470.2251-0.1357-0.309-0.05880.23270.03420.00610.24880.02090.244819.83497.335710.092
202.31341.59711.27956.1713.56475.27560.2160.12-0.2-0.4679-0.46280.91740.1827-0.53810.19550.28450.0488-0.10540.3306-0.04290.378220.9520.0873-8.5445
210.1188-0.11980.12641.7458-0.8381.17110.06480.0145-0.0373-0.10950.02340.17160.0984-0.0932-0.09410.1955-0.0028-0.00560.2356-0.01260.235331.6444-12.84695.6151
224.3855-3.68810.80563.6192-0.9080.78040.42940.4932-0.8174-0.5126-0.30280.58120.3354-0.0902-0.09380.3866-0.0177-0.03020.385-0.09670.425224.1183-27.49526.6363
231.15470.02650.56811.2433-0.27021.1740.03740.0945-0.0108-0.1412-0.0513-0.05660.00380.16470.01190.22480.00530.01210.2270.0050.201335.9619-7.58584.9282
242.4081-2.22840.69817.9194-2.39364.23280.20690.2735-0.1269-0.6032-0.05120.08630.2956-0.105-0.15320.4320.0338-0.03340.3119-0.0650.270433.1383-14.2812-11.491
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1( CHAIN A AND RESID 1:20 )A1 - 20
2X-RAY DIFFRACTION2( CHAIN A AND ( RESID 21:93 OR RESID 801:801 ) )A21 - 93
3X-RAY DIFFRACTION2( CHAIN A AND ( RESID 21:93 OR RESID 801:801 ) )A801
4X-RAY DIFFRACTION3( CHAIN A AND RESID 94:126 )A94 - 126
5X-RAY DIFFRACTION4( CHAIN A AND ( RESID 127:213 OR RESID 804:804 ) )A127 - 213
6X-RAY DIFFRACTION4( CHAIN A AND ( RESID 127:213 OR RESID 804:804 ) )A804
7X-RAY DIFFRACTION5( CHAIN A AND RESID 214:275 )A214 - 275
8X-RAY DIFFRACTION6( CHAIN A AND RESID 276:331 )A276 - 331
9X-RAY DIFFRACTION7( CHAIN B AND RESID 1:20 )B1 - 20
10X-RAY DIFFRACTION8( CHAIN B AND ( RESID 21:93 OR RESID 801:801 ) )B21 - 93
11X-RAY DIFFRACTION8( CHAIN B AND ( RESID 21:93 OR RESID 801:801 ) )B801
12X-RAY DIFFRACTION9( CHAIN B AND RESID 94:126 )B94 - 126
13X-RAY DIFFRACTION10( CHAIN B AND ( RESID 127:225 OR RESID 803:803 ) )B127 - 225
14X-RAY DIFFRACTION10( CHAIN B AND ( RESID 127:225 OR RESID 803:803 ) )B803
15X-RAY DIFFRACTION11( CHAIN B AND RESID 226:244 )B226 - 244
16X-RAY DIFFRACTION12( CHAIN B AND RESID 245:331 )B245 - 331
17X-RAY DIFFRACTION13( CHAIN C AND RESID 1:20 )C1 - 20
18X-RAY DIFFRACTION14( CHAIN C AND ( RESID 21:93 OR RESID 801:801 ) )C21 - 93
19X-RAY DIFFRACTION14( CHAIN C AND ( RESID 21:93 OR RESID 801:801 ) )C801
20X-RAY DIFFRACTION15( CHAIN C AND RESID 94:126 )C94 - 126
21X-RAY DIFFRACTION16( CHAIN C AND ( RESID 127:308 OR RESID 804:804 ) )C127 - 308
22X-RAY DIFFRACTION16( CHAIN C AND ( RESID 127:308 OR RESID 804:804 ) )C804
23X-RAY DIFFRACTION17( CHAIN C AND RESID 309:331 )C309 - 331
24X-RAY DIFFRACTION18( CHAIN D AND RESID 1:20 )D1 - 20
25X-RAY DIFFRACTION19( CHAIN D AND ( RESID 21:93 OR RESID 801:801 ) )D21 - 93
26X-RAY DIFFRACTION19( CHAIN D AND ( RESID 21:93 OR RESID 801:801 ) )D801
27X-RAY DIFFRACTION20( CHAIN D AND RESID 94:126 )D94 - 126
28X-RAY DIFFRACTION21( CHAIN D AND ( RESID 127:213 OR RESID 803:803 ) )D127 - 213
29X-RAY DIFFRACTION21( CHAIN D AND ( RESID 127:213 OR RESID 803:803 ) )D803
30X-RAY DIFFRACTION22( CHAIN D AND RESID 214:244 )D214 - 244
31X-RAY DIFFRACTION23( CHAIN D AND RESID 245:308 )D245 - 308
32X-RAY DIFFRACTION24( CHAIN D AND RESID 309:331 )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