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1E9N

A second divalent metal ion in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1, and its implications for the catalytic mechanism

Functional Information from GO Data
ChainGOidnamespacecontents
A0000723biological_processtelomere maintenance
A0000781cellular_componentchromosome, telomeric region
A0003677molecular_functionDNA binding
A0003684molecular_functiondamaged DNA binding
A0003691molecular_functiondouble-stranded telomeric DNA binding
A0003713molecular_functiontranscription coactivator activity
A0003714molecular_functiontranscription corepressor activity
A0003723molecular_functionRNA binding
A0003824molecular_functioncatalytic activity
A0003906molecular_functionDNA-(apurinic or apyrimidinic site) endonuclease activity
A0004518molecular_functionnuclease activity
A0004519molecular_functionendonuclease activity
A0004520molecular_functionDNA endonuclease activity
A0004523molecular_functionRNA-DNA hybrid ribonuclease activity
A0004527molecular_functionexonuclease activity
A0004528molecular_functionphosphodiesterase I activity
A0004844molecular_functionuracil DNA N-glycosylase activity
A0005515molecular_functionprotein binding
A0005634cellular_componentnucleus
A0005654cellular_componentnucleoplasm
A0005730cellular_componentnucleolus
A0005737cellular_componentcytoplasm
A0005739cellular_componentmitochondrion
A0005783cellular_componentendoplasmic reticulum
A0005813cellular_componentcentrosome
A0005840cellular_componentribosome
A0006281biological_processDNA repair
A0006284biological_processbase-excision repair
A0006287biological_processbase-excision repair, gap-filling
A0006308biological_processDNA catabolic process
A0006310biological_processDNA recombination
A0006974biological_processDNA damage response
A0008081molecular_functionphosphoric diester hydrolase activity
A0008296molecular_function3'-5'-DNA exonuclease activity
A0008309molecular_functiondouble-stranded DNA exodeoxyribonuclease activity
A0008311molecular_functiondouble-stranded DNA 3'-5' DNA exonuclease activity
A0008408molecular_function3'-5' exonuclease activity
A0016491molecular_functionoxidoreductase activity
A0016607cellular_componentnuclear speck
A0016787molecular_functionhydrolase activity
A0016890molecular_functionsite-specific endodeoxyribonuclease activity, specific for altered base
A0031490molecular_functionchromatin DNA binding
A0042981biological_processregulation of apoptotic process
A0043488biological_processregulation of mRNA stability
A0044029biological_processpositive regulation of gene expression via chromosomal CpG island demethylation
A0045454biological_processcell redox homeostasis
A0045892biological_processnegative regulation of DNA-templated transcription
A0045944biological_processpositive regulation of transcription by RNA polymerase II
A0046872molecular_functionmetal ion binding
A0048471cellular_componentperinuclear region of cytoplasm
A0052720molecular_functionclass II DNA-(apurinic or apyrimidinic site) endonuclease activity
A0090580molecular_functionphosphodiesterase activity, acting on 3'-phosphoglycolate-terminated DNA strands
A0097698biological_processtelomere maintenance via base-excision repair
A0140431molecular_functionDNA-(abasic site) binding
B0000723biological_processtelomere maintenance
B0000781cellular_componentchromosome, telomeric region
B0003677molecular_functionDNA binding
B0003684molecular_functiondamaged DNA binding
B0003691molecular_functiondouble-stranded telomeric DNA binding
B0003713molecular_functiontranscription coactivator activity
B0003714molecular_functiontranscription corepressor activity
B0003723molecular_functionRNA binding
B0003824molecular_functioncatalytic activity
B0003906molecular_functionDNA-(apurinic or apyrimidinic site) endonuclease activity
B0004518molecular_functionnuclease activity
B0004519molecular_functionendonuclease activity
B0004520molecular_functionDNA endonuclease activity
B0004523molecular_functionRNA-DNA hybrid ribonuclease activity
B0004527molecular_functionexonuclease activity
B0004528molecular_functionphosphodiesterase I activity
B0004844molecular_functionuracil DNA N-glycosylase activity
B0005515molecular_functionprotein binding
B0005634cellular_componentnucleus
B0005654cellular_componentnucleoplasm
B0005730cellular_componentnucleolus
B0005737cellular_componentcytoplasm
B0005739cellular_componentmitochondrion
B0005783cellular_componentendoplasmic reticulum
B0005813cellular_componentcentrosome
B0005840cellular_componentribosome
B0006281biological_processDNA repair
B0006284biological_processbase-excision repair
B0006287biological_processbase-excision repair, gap-filling
B0006308biological_processDNA catabolic process
B0006310biological_processDNA recombination
B0006974biological_processDNA damage response
B0008081molecular_functionphosphoric diester hydrolase activity
B0008296molecular_function3'-5'-DNA exonuclease activity
B0008309molecular_functiondouble-stranded DNA exodeoxyribonuclease activity
B0008311molecular_functiondouble-stranded DNA 3'-5' DNA exonuclease activity
B0008408molecular_function3'-5' exonuclease activity
B0016491molecular_functionoxidoreductase activity
B0016607cellular_componentnuclear speck
B0016787molecular_functionhydrolase activity
B0016890molecular_functionsite-specific endodeoxyribonuclease activity, specific for altered base
B0031490molecular_functionchromatin DNA binding
B0042981biological_processregulation of apoptotic process
B0043488biological_processregulation of mRNA stability
B0044029biological_processpositive regulation of gene expression via chromosomal CpG island demethylation
B0045454biological_processcell redox homeostasis
B0045892biological_processnegative regulation of DNA-templated transcription
B0045944biological_processpositive regulation of transcription by RNA polymerase II
B0046872molecular_functionmetal ion binding
B0048471cellular_componentperinuclear region of cytoplasm
B0052720molecular_functionclass II DNA-(apurinic or apyrimidinic site) endonuclease activity
B0090580molecular_functionphosphodiesterase activity, acting on 3'-phosphoglycolate-terminated DNA strands
B0097698biological_processtelomere maintenance via base-excision repair
B0140431molecular_functionDNA-(abasic site) binding
Functional Information from PDB Data
site_idAC1
Number of Residues3
DetailsBINDING SITE FOR RESIDUE PB A1319
ChainResidue
AASP70
AGLU96
AHOH2164

site_idAC2
Number of Residues4
DetailsBINDING SITE FOR RESIDUE PB A1320
ChainResidue
AASP210
AASN212
AHIS309
AHOH2080

site_idAC3
Number of Residues4
DetailsBINDING SITE FOR RESIDUE PB B1319
ChainResidue
BLEU282
BHIS309
BASP210
BASN212

site_idAC4
Number of Residues2
DetailsBINDING SITE FOR RESIDUE PB B1320
ChainResidue
BGLU96
BHOH2178

Functional Information from PROSITE/UniProt
site_idPS00726
Number of Residues10
DetailsAP_NUCLEASE_F1_1 AP endonucleases family 1 signature 1. PDILCLQETK
ChainResidueDetails
APRO89-LYS98

site_idPS00727
Number of Residues17
DetailsAP_NUCLEASE_F1_2 AP endonucleases family 1 signature 2. DSFRHlypntpyaYTFW
ChainResidueDetails
AASP251-TRP267

site_idPS00728
Number of Residues12
DetailsAP_NUCLEASE_F1_3 AP endonucleases family 1 signature 3. NvGwRLDYfLlS
ChainResidueDetails
AASN277-SER288

Functional Information from SwissProt/UniProt
site_idSWS_FT_FI1
Number of Residues2
DetailsACT_SITE: ACT_SITE => ECO:0000269|PubMed:15380100
ChainResidueDetails
AVAL172
BVAL172

site_idSWS_FT_FI2
Number of Residues2
DetailsACT_SITE: Proton donor/acceptor => ECO:0000269|PubMed:9351835, ECO:0007744|PDB:1BIX
ChainResidueDetails
ALEU211
BLEU211

site_idSWS_FT_FI3
Number of Residues2
DetailsACT_SITE: Proton acceptor => ECO:0000255|PROSITE-ProRule:PRU00764
ChainResidueDetails
ACYS310
BCYS310

site_idSWS_FT_FI4
Number of Residues12
DetailsBINDING: BINDING => ECO:0000255|PROSITE-ProRule:PRU00764
ChainResidueDetails
AVAL69
BVAL213
BHIS309
BCYS310
ATHR97
ALEU211
AVAL213
AHIS309
ACYS310
BVAL69
BTHR97
BLEU211

site_idSWS_FT_FI5
Number of Residues2
DetailsSITE: Cleavage; by granzyme A
ChainResidueDetails
ALYS32
BLYS32

site_idSWS_FT_FI6
Number of Residues2
DetailsSITE: Transition state stabilizer => ECO:0000269|PubMed:8932375
ChainResidueDetails
AVAL213
BVAL213

site_idSWS_FT_FI7
Number of Residues2
DetailsSITE: Important for catalytic activity => ECO:0000269|PubMed:21762700, ECO:0000269|PubMed:9804799
ChainResidueDetails
ATYR284
BTYR284

site_idSWS_FT_FI8
Number of Residues2
DetailsSITE: Interaction with DNA substrate
ChainResidueDetails
ACYS310
BCYS310

site_idSWS_FT_FI9
Number of Residues4
DetailsMOD_RES: N6-acetyllysine; by EP300 => ECO:0000269|PubMed:14633989
ChainResidueDetails
ALYS7
AGLY8
BLYS7
BGLY8

site_idSWS_FT_FI10
Number of Residues8
DetailsMOD_RES: N6-acetyllysine => ECO:0000269|PubMed:20699270
ChainResidueDetails
ATHR28
ALYS32
AASN33
AGLU36
BTHR28
BLYS32
BASN33
BGLU36

site_idSWS_FT_FI11
Number of Residues2
DetailsMOD_RES: Phosphoserine => ECO:0007744|PubMed:23186163
ChainResidueDetails
APRO55
BPRO55

site_idSWS_FT_FI12
Number of Residues4
DetailsMOD_RES: S-nitrosocysteine; alternate => ECO:0000269|PubMed:17403694
ChainResidueDetails
ASER66
ALEU94
BSER66
BLEU94

site_idSWS_FT_FI13
Number of Residues2
DetailsMOD_RES: N6-acetyllysine => ECO:0007744|PubMed:19608861
ChainResidueDetails
AGLY198
BGLY198

site_idSWS_FT_FI14
Number of Residues2
DetailsMOD_RES: Phosphothreonine; by CDK5 => ECO:0000250|UniProtKB:P28352
ChainResidueDetails
APRO234
BPRO234

site_idSWS_FT_FI15
Number of Residues2
DetailsMOD_RES: S-nitrosocysteine => ECO:0000269|PubMed:17403694
ChainResidueDetails
APRO311
BPRO311

Catalytic Information from CSA
site_idMCSA1
Number of Residues8
DetailsM-CSA 510
ChainResidueDetails
AGLY71metal ligand
ATHR97metal ligand
AVAL172electrostatic stabiliser, metal ligand
ALEU211increase nucleophilicity, metal ligand, proton acceptor
AVAL213
ATYR284electrostatic stabiliser
AHIS309metal ligand
ACYS310electrostatic stabiliser, metal ligand

site_idMCSA2
Number of Residues8
DetailsM-CSA 510
ChainResidueDetails
BGLY71metal ligand
BTHR97metal ligand
BVAL172electrostatic stabiliser, metal ligand
BLEU211increase nucleophilicity, metal ligand, proton acceptor
BVAL213
BTYR284electrostatic stabiliser
BHIS309metal ligand
BCYS310electrostatic stabiliser, metal ligand

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PDB entries from 2024-04-24

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