1D3G

HUMAN DIHYDROOROTATE DEHYDROGENASE COMPLEXED WITH BREQUINAR ANALOG

> Summary

Summary for 1D3G

Related1D3H
DescriptorDIHYDROOROTATE DEHYDROGENASE (1.3.3.1)
Functional Keywordsprotein-antiproliferative agent complex, oxidoreductase
Biological sourceHomo sapiens (human)
Cellular locationMitochondrion inner membrane; Single-pass membrane protein Q02127
Total number of polymer chains1
Total molecular weight41183.22
Authors
Liu, S.,Neidhardt, E.A.,Grossman, T.H.,Ocain, T.,Clardy, J. (deposition date: 1999-09-29, release date: 2000-09-13, modification date: 2009-02-24)
Primary citation
Liu, S.,Neidhardt, E.A.,Grossman, T.H.,Ocain, T.,Clardy, J.
Structures of human dihydroorotate dehydrogenase in complex with antiproliferative agents.
Structure Fold.Des., 8:25-33, 2000
PubMed: 10673429
DOI: 10.1016/S0969-2126(00)00077-0
MImport into Mendeley
Experimental method
X-RAY DIFFRACTION (1.6 Å)
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Structure validation

RfreeClashscoreRamachandran outliersSidechain outliersRSRZ outliers0.18450.3%1.4%6.1%MetricValuePercentile RanksWorseBetterPercentile relative to all X-ray structuresPercentile relative to X-ray structures of similar resolution

More Asymmetric unit images

Molmil generated image of 1d3g
no rotation
Molmil generated image of 1d3g
rotated about x axis by 90°
Molmil generated image of 1d3g
rotated about y axis by 90°

> Structural details

Entity

Chain IDDescriptionTypeChain lengthFormula weightNumber of moleculesDB Name (Accession)Biological sourceDescriptive keywords
ADIHYDROOROTATE DEHYDROGENASEpolymer36739856.91
UniProt (Q02127)
Pfam (PF01180)
Homo sapiens (human)@PDBj
SULFATE IONnon-polymer96.11
ACETATE IONnon-polymer59.01
2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACIDnon-polymer357.41
FLAVIN MONONUCLEOTIDEnon-polymer456.31
OROTIC ACIDnon-polymer156.11
DECYLAMINE-N,N-DIMETHYL-N-OXIDEnon-polymer201.41
waterwater18.0274

Sequence viewer

Contents of the asymmetric unit

PolymersNumber of chains1
Total molecular weight39856.9
Non-Polymers*Number of molecules6
Total molecular weight1326.3
All*Total molecular weight41183.2
*Water molecules are not included.

> Experimental details

Refinement Statistics

Experimental method:X-RAY DIFFRACTION (1.6 Å)

Cell axes90.61090.610122.410
Cell angles90.0090.00120.00
SpacegroupP 32 2 1
Resolution limits30.00 - 1.60
the highest resolution shell value1.700 - 1.600
R-factor0.169*
R-work0.16800
the highest resolution shell value0.166
R-free0.18800
the highest resolution shell value0.194
RMSD bond length0.009*
RMSD bond angle1.800 (2.000*)

Data Collection Statistics

Resolution limits30.00 - 1.60
the highest resolution shell value -
Number of reflections75457
Number of measurements444987*
Rmerge_l_obs0.040
the highest resolution shell value0.210
Completeness97.0 (97.1*)
the highest resolution shell value84.8*
Redundancy5.9
the highest resolution shell value3.2
I/sigma(I)0

Crystallization Conditions

crystal IDmethodpHpH rangetemperatureunit
1VAPOR DIFFUSION (Vapor diffusion, hanging drop*)293 (20*)*

Crystallization Reagents

IDcrystal IDsolution IDreagent nameconcentrationdetails
Crystallization Reagents in Literatures*
IDcrystal IDsolutionreagent nameconcentration (unit)details
11dropprotein10 (mg/ml)
21drop25 (mM)
31drop200 (mM)
41dropglycerol15 (%)
51dropEDTA0.5 (mM)
61dropHEPES25 (mM)
71dropacetate0.05 (M)
81dropDDAO10.4 (mM)
91dropDHO1 (mM)
101dropammonium sulfate1.2-1.3 (M)
111dropBrequinar0.5 (mM)
121reservoiracetate0.1 (M)
131reservoirammonium sulfate2.4-2.6 (M)
141reservoirglycerol30 (%)
Annotated Information is extracted from Literature Info*

> Functional details

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Functional Information from GO Data

ChainGOidnamespacecontents
A0005737cellular_componentcytoplasm
A0016021cellular_componentintegral component of membrane
A0005743cellular_componentmitochondrial inner membrane
A0005739cellular_componentmitochondrion
A0043025cellular_componentneuronal cell body
A0005654cellular_componentnucleoplasm
A0004152molecular_functiondihydroorotate dehydrogenase activity
A0008144molecular_functiondrug binding
A0010181molecular_functionFMN binding
A0048039molecular_functionubiquinone binding
A0006207biological_process'de novo' pyrimidine nucleobase biosynthetic process
A0044205biological_process'de novo' UMP biosynthetic process
A0007565biological_processfemale pregnancy
A0007595biological_processlactation
A0043065biological_processpositive regulation of apoptotic process
A0046134biological_processpyrimidine nucleoside biosynthetic process
A0090140biological_processregulation of mitochondrial fission
A0031000biological_processresponse to caffeine
A0042493biological_processresponse to drug
A0042594biological_processresponse to starvation
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Functional Information from PDB Data

site_idNumber of ResiduesDetails
AC14BINDING SITE FOR RESIDUE SO4 A 400
ChainResidue
AARG216
AVAL218
AHIS219
AHOH

AC27BINDING SITE FOR RESIDUE ACT A 401
ChainResidue
ALYS278
APRO279
AASP282
ATHR285
AGLN286
AARG289
AHOH

AC314BINDING SITE FOR RESIDUE BRE A 397
ChainResidue
ALEU17
AGLN18
APRO23
AALA26
AHIS27
AALA30
ALEU38
ALEU39
AVAL105
AARG107
ATYR327
ATHR331
AHOH
ADDQ

AC425BINDING SITE FOR RESIDUE FMN A 398
ChainResidue
AALA66
AALA67
AGLY68
ALYS71
AGLY90
ASER91
AASN116
AASN152
AASN183
ALYS226
ATHR254
AASN255
ATHR256
ASER276
AGLY277
ALEU280
AVAL304
AGLY305
AGLY306
ALEU326
ATYR327
ATHR328
AORO
AHOH
AHOH

AC511BINDING SITE FOR RESIDUE ORO A 399
ChainResidue
ALYS71
AASN116
ATYR118
AGLY119
APHE120
AASN183
ASER186
AASN188
AASN255
ATHR256
AFMN

AC67BINDING SITE FOR RESIDUE DDQ A 700
ChainResidue
AMET1
AALA2
ATYR9
ALEU29
APHE33
ALEU39
ABRE

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Functional Information from PDB atom coordinates for the "HETATM" binding sites

site_idNumber of ResiduesDetails
DDQ_1d3g_A_70012DECYLAMINE-N,N-DIMETHYL-N-OXIDE binding site
ChainResidueligand
AMET30-ALA31DDQ: DECYLAMINE-N,N-DIMETHYL-N-OXIDE
ATYR38DDQ: DECYLAMINE-N,N-DIMETHYL-N-OXIDE
ALEU42DDQ: DECYLAMINE-N,N-DIMETHYL-N-OXIDE
ALEU46DDQ: DECYLAMINE-N,N-DIMETHYL-N-OXIDE
ALEU58-ALA59DDQ: DECYLAMINE-N,N-DIMETHYL-N-OXIDE
APHE62DDQ: DECYLAMINE-N,N-DIMETHYL-N-OXIDE
AGLY66-PRO69DDQ: DECYLAMINE-N,N-DIMETHYL-N-OXIDE

BRE_1d3g_A_397262-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID binding site
ChainResidueligand
ATYR38BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
ALEU42-MET43BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
ALEU46-GLN47BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
ALEU50-PRO52BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
AALA55-HIS56BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
AALA59BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
APHE62-THR63BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
ALEU67-PRO69BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
APHE98BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
AMET111BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
AVAL134BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
AARG136BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
AVAL143BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
ATYR356BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
ALEU359-THR360BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID
AGLY363-PRO364BRE: 2-BIPHENYL-4-YL-6-FLUORO-3-METHYL-QUINOLINE-4-CARBOXYLIC ACID

FMN_1d3g_A_39830FLAVIN MONONUCLEOTIDE binding site
ChainResidueligand
AALA95-GLY97FMN: FLAVIN MONONUCLEOTIDE
ALYS100FMN: FLAVIN MONONUCLEOTIDE
AGLU117FMN: FLAVIN MONONUCLEOTIDE
AGLY119-SER120FMN: FLAVIN MONONUCLEOTIDE
AVAL134FMN: FLAVIN MONONUCLEOTIDE
AVAL143FMN: FLAVIN MONONUCLEOTIDE
AASN145FMN: FLAVIN MONONUCLEOTIDE
ATYR147FMN: FLAVIN MONONUCLEOTIDE
APHE149FMN: FLAVIN MONONUCLEOTIDE
AASN181FMN: FLAVIN MONONUCLEOTIDE
AASN212FMN: FLAVIN MONONUCLEOTIDE
ALYS255FMN: FLAVIN MONONUCLEOTIDE
ATHR283-THR285FMN: FLAVIN MONONUCLEOTIDE
ASER305-GLY306FMN: FLAVIN MONONUCLEOTIDE
ALEU309FMN: FLAVIN MONONUCLEOTIDE
AVAL333-VAL336FMN: FLAVIN MONONUCLEOTIDE
AGLN354-ALA358FMN: FLAVIN MONONUCLEOTIDE

ORO_1d3g_A_39916OROTIC ACID binding site
ChainResidueligand
ALYS100ORO: OROTIC ACID
ASER120ORO: OROTIC ACID
AASN145-ASN150ORO: OROTIC ACID
AASN212ORO: OROTIC ACID
ASER214-ASN217ORO: OROTIC ACID
AASN284-THR285ORO: OROTIC ACID
AGLY303ORO: OROTIC ACID

ACT_1d3g_A_4014ACETATE ION binding site
ChainResidueligand
AASP311ACT: ACETATE ION
ATHR314-GLN315ACT: ACETATE ION
AARG318ACT: ACETATE ION

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Functional Information from PROSITE/UniProt

site_idNumber of ResiduesDetails
PS009121Dihydroorotate dehydrogenase signature 2. [LIVM](2)-[GSA]-x-G-G-[IV]-x-[STGDN]-x(3)-[ACV]-x(2)-{A}-{R}-x-{L}-G-A
ChainResidueDetails
ANA*

PS009111Dihydroorotate dehydrogenase signature 1. [GSA]-x(4)-[GK]-[GSTA]-[LIVFSTA]-[GST]-x(3)-[NQRK]-x-G-[NHY]-x(2)-P
ChainResidueDetails
ANA*

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Functional Information from SwissProt/UniProt

site_idNumber of ResiduesDetails
SWS_FT_FI11Nucleophile.
ChainResidueDetails
ASER186

SWS_FT_FI21FMN; via carbonyl oxygen.
ChainResidueDetails
ATHR254

SWS_FT_FI32FMN; via amide nitrogen.
ChainResidueDetails
AGLY277
AGLY306

SWS_FT_FI41Substrate.
ChainResidueDetails
ALYS71

SWS_FT_FI54FMN.
ChainResidueDetails
ASER91
AASN152
AASN183
ALYS226

SWS_FT_FI62FMN.
ChainResidueDetails
ANA*
ANA*

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Catalytic Information from CSA

site_idNumber of ResiduesDetails
CSA14a catalytic site defined by CSA, PubMed 10673429
ChainResidueDetails
ASER215
ATHR218
APHE149
ALYS255

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Catalytic Information from CATRES

site_idNumber of ResiduesDetails

> Sequence Neighbor

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