1TDH


Conserved Protein Domain Family
MeNeil1_N

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cd08967: MeNeil1_N 
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N-terminal domain of metazoan Nei-like glycosylase 1 (NEIL1)
This family contains the N-terminal domain of metazoan NEIL1. It belongs to the FpgNei_N, [N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII)] domain superfamily. DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. They initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycosylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. NEIL1 recognizes the oxidized pyrimidines 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) and 4,6-diamino- 5-formamidopyrimidine (FapyA), thymine glycol (Tg) and 5-hydroxyuracil (5-OHU). However, even though it has weak activity on 8-oxo-7,8-dihydroguanine (8-oxoG), it does show strong preference for the products of its further oxidation: spiroiminodihydantoin and guanidinohydantoin. In addition to this MeNeil1_N domain, enzymes belonging to this family contain a helix-two turn-helix (H2TH) domain and a zincless finger motif. This characteristic "zincless finger" motif, is a structural equivalent of the zinc finger common to other members of the Fpg/Nei family. Neil1 is one of three homologs found in eukaryotes and its lineage extends back as far as early metazoans.
Statistics
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PSSM-Id: 176801
View PSSM: cd08967
Aligned: 7 rows
Threshold Bit Score: 223.107
Threshold Setting Gi: 221115178
Author:
Barrantes-Reynolds
Author Information
Name: Ramiro Barrantes-Reynolds
Address: Department of Microbiology and Molecular Genetics
University of Vermont
89 Beaumont Avenue
Burlington, VT 05405
USA
Created: 4-Jul-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site include 1 residue -Click on image for an interactive view with Cn3D
Feature 1:catalytic residue [active site]
Evidence:
  • Comment:This catalytic proline is almost perfectly conserved in FpgNei DNA glycolsylases. It acts as a nucleophile in catalysis.
  • Citation:PMID 9030608
  • Comment:Site-directed mutagenesis of this residue renders Fpg proteins defective in catalysis but still able to make the Schiff-base intermediate.
  • Citation:PMID 9654091
  • Comment:Site-directed mutagensis of this residue renders Escherichia coli Nei inactive but still able to make the Schiff-base intermediate.
  • Comment:1KFV_A , is a structure of a mutant Lactococcus Lactis Fpg which has a Gly in place of a Pro at this position.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1         #                                                                              
1TDH_A         1 MPEGPELHLASQFVNEaCRALVFGGCVEKSSVS-RNP--EVPFesSAYRISASARGKELRLILSPlpga----------- 66  human
AAH74457       1 MPEGPELHRASLFVNKvCKGLSFAGAVEKSAVS-KNT--DVPFscPEYTISSVSRGKEVKLILTPlsd------------ 65  African clawed ...
AAQ97820       1 MPEGPELHLASLFVNRmCEGVVFTGAVEKSEVN-KNP--EVPFccDAYCIKAQSRGKEVRLTLTPikndasskr------ 71  zebrafish
XP_002110397   1 MPEGPEVRLASDYINHiCCNVIFSGQIVKSDVS-KNP--SITFaaPFYTITGQSRGKELLLTLKEadanngnseem---- 73  Trichoplax adha...
XP_001629836   1 MPEGPELHKAALLVNTmCKGRVFTGKIKKSAANyKNP--EVEHnyKEYTIRAESRGKEMAVILSGyplandk-------- 70  starlet sea ane...
XP_002166096   1 MPEGPEHYLASDFINQsCNGKIFSGNVLKSSVT-KNPciELPF--KHFLISAESRGKELMLKLSEfyekdikmdlelhnq 77  green hydra
CAF98335       1 MPEGPELHLASLYVNKmCQGLIFTGAVRKSEVS-KAP--DVPFtcEAYRITAASRGKEVKLTLTPmks------------ 65  spotted green p...
Feature 1                                                                                        
1TDH_A        67 ------------------qpqqEPLALVFRFGMSGSFQLVPrEELPRHAHLRFYTAPPGPr--LALCFVDiRRFGRWDLG 126 human
AAH74457      66 --------------------esEETHIVFRFGMSGSFKFTPqDQIPKHAHLRFYTKDSPQ---RVLCFVDpRRFGTWEVH 122 African clawed ...
AAQ97820      72 --------------kiderqsqQPMNVVFRFGMSGFFRFTSvDELPKHAHLRFYTNETPH---RVLSFEDtRRFGSWQPN 134 zebrafish
XP_002110397  74 -----------nhrvkkecdsrLEMRILFGFGMSGSFSVTDsDNIPKHSHLRFYAHNKSS---MVLNFVDpRRFGTWRVT 139 Trichoplax adha...
XP_001629836  71 ----------------krakknGDLRILFRFGMSGRFQFGPvDEMHKHAHLNFYTKTEKKdkgLVLSFVDvRRFGGWQVK 134 starlet sea ane...
XP_002166096  78 sikfeeinvekqdqstfqnkilSEVKILFQFGMSGTFTFTSeADIPKHSHLKFYTFEEPK---MVLSFVDiRRFGKWKIS 154 green hydra
CAF98335      66 -------------------qgdQPMDIVFRFGMSGYFRLTTeDELPKHSHLRFYSNEEPC---RVLSFVDtRSFGSWQPG 123 spotted green p...
Feature 1         
1TDH_A       127 G 127 human
AAH74457     123 G 123 African clawed frog
AAQ97820     135 G 135 zebrafish
XP_002110397 140 N 140 Trichoplax adhaerens
XP_001629836 135 D 135 starlet sea anemone
XP_002166096 155 D 155 green hydra
CAF98335     124 G 124 spotted green pufferfish

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