Target type: molecularfunction
Catalysis of the cleavage of an AP site 3' of the baseless site by a beta-lyase mechanism, leaving an unsaturated aldehyde, termed a 3'-(4-hydroxy-5-phospho-2-pentenal) residue, and a 5'-phosphate. [PMID:1698278, RHEA:66592]
Class I DNA-(apurinic or apyrimidinic site) endonuclease activity is a crucial molecular function involved in the repair of damaged DNA. DNA can be damaged by various factors, including exposure to radiation, reactive oxygen species, and environmental mutagens. One common type of damage is the loss of a purine or pyrimidine base from the DNA backbone, resulting in an abasic site (also known as an AP site). These AP sites disrupt the DNA structure and can lead to mutations or cell death if left unrepaired.
Class I DNA-(apurinic or apyrimidinic site) endonucleases are a family of enzymes that specifically recognize and cleave the phosphodiester backbone of DNA at or near AP sites. Their primary function is to remove the damaged portion of the DNA, providing a free 3'-hydroxyl group for subsequent DNA repair processes.
The mechanism of action of Class I DNA-(apurinic or apyrimidinic site) endonucleases involves the following steps:
1. **Recognition of the AP site:** The enzyme recognizes the AP site through interactions with the distorted DNA structure caused by the missing base.
2. **Cleavage of the phosphodiester backbone:** The enzyme cleaves the phosphodiester bond 5' to the AP site, generating a 5'-deoxyribose phosphate group and a 3'-hydroxyl group.
3. **Release of the damaged DNA fragment:** The enzyme releases the damaged DNA fragment, leaving a single-stranded gap in the DNA.
This process allows for the removal of the damaged DNA segment, providing a substrate for other repair pathways, such as base excision repair (BER) or nucleotide excision repair (NER). These pathways can then fill the gap with the correct nucleotide sequence, restoring the integrity of the DNA.
In summary, Class I DNA-(apurinic or apyrimidinic site) endonucleases play a vital role in maintaining genomic stability by recognizing and removing damaged DNA segments containing AP sites, ensuring accurate DNA replication and preventing mutations.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Formamidopyrimidine-DNA glycosylase | A formamidopyrimidine-DNA glycosylase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P05523] | Escherichia coli K-12 |
| Endonuclease 8-like 1 | An endonuclease 8-like 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q96FI4] | Homo sapiens (human) |
| Endonuclease III-like protein 1 | An endonuclease III-like protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P78549] | Homo sapiens (human) |
| 40S ribosomal protein S3 | A eukaryotic-type small ribosomal subunit protein uS3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P23396] | Homo sapiens (human) |
| DNA polymerase beta | A DNA polymerase beta that is encoded in the genome of human. [PRO:CNA] | Homo sapiens (human) |
| N-glycosylase/DNA lyase | An N-glycosylase/DNA lyase that is encoded in the genome of human. [PRO:DNx, UniProtKB:O15527] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| digallic acid | digallic acid: structure given in first source | benzoate ester; gallate ester | |
| hydralazine | hydralazine : The 1-hydrazino derivative of phthalazine; a direct-acting vasodilator that is used as an antihypertensive agent. Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. | azaarene; hydrazines; ortho-fused heteroarene; phthalazines | antihypertensive agent; vasodilator agent |
| isocarboxazid | Isocarboxazid: An MAO inhibitor that is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in the treatment of panic disorder and the phobic disorders. (From AMA, Drug Evaluations Annual, 1994, p311) | benzenes | |
| isoniazid | Hydra: A genus of freshwater polyps in the family Hydridae, order Hydroida, class HYDROZOA. They are of special interest because of their complex organization and because their adult organization corresponds roughly to the gastrula of higher animals. hydrazide : Compounds derived from oxoacids RkE(=O)l(OH)m (l =/= 0) by replacing -OH by -NRNR2 (R groups are commonly H). (IUPAC). | carbohydrazide | antitubercular agent; drug allergen |
| nialamide | Nialamide: An MAO inhibitor that is used as an antidepressive agent. | organonitrogen compound; organooxygen compound | |
| pamoic acid | pamoic acid: RN given refers to parent cpd; structure | dicarboxylic acid | |
| hydralazine hydrochloride | hydralazine hydrochloride : The hydrochloride salt of hydralazine; a direct-acting vasodilator that is used as an antihypertensive agent. | hydrochloride | antihypertensive agent; vasodilator agent |
| Dillapiole | 5-allyl 6,7-dimethoxy 1,3-benzodioxole: a plant based insecticide; structure in first source | benzodioxoles | metabolite |
| oleanolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | plant metabolite | |
| zidovudine | zidovudine : A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase. Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. | azide; pyrimidine 2',3'-dideoxyribonucleoside | antimetabolite; antiviral drug; HIV-1 reverse transcriptase inhibitor |
| ursolic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | geroprotector; plant metabolite | |
| thymidine 5'-triphosphate | dTTP : A thymidine phosphate having a triphosphate group at the 5'-position. thymidine 5'-triphosphate: RN given refers to parent cpd | pyrimidine 2'-deoxyribonucleoside 5'-triphosphate; thymidine phosphate | Escherichia coli metabolite; mouse metabolite |
| betulinic acid | hydroxy monocarboxylic acid; pentacyclic triterpenoid | anti-HIV agent; anti-inflammatory agent; antimalarial; antineoplastic agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; plant metabolite | |
| calanolide a | (+)-calanolide A : An organic heterotetracyclic compound that is 11,12-dihydro-2H,6H,10H-dipyrano[2,3-f:2',3'-h]chromen-2-one substituted by a hydroxy group at position 12, methyl groups at positions 6, 6, 10 and 11 and a propyl group at position 4 (the 10R,11S,12S stereoisomer). Isolated from Calophyllum lanigerum var austrocoriaceum and Calophyllum brasiliense, it exhibits potent activity against HIV-1 reverse transcriptase. calanolide A: NSC 661122 and costatolide are isomers; a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum (Clusiaceae); structure in first source | cyclic ether; delta-lactone; organic heterotetracyclic compound; secondary alcohol | HIV-1 reverse transcriptase inhibitor; plant metabolite |
| 2',3'-dideoxythymidine triphosphate | ddTTP : A pyrimidine 2',3'-dideoxyribonucleoside 5'-triphosphate having thymine as the nucleobase. | pyrimidine 2',3'-dideoxyribonucleoside 5'-triphosphate; thymidine phosphate | |
| 2',3'-dideoxyadenosine triphosphate | purine deoxyribonucleoside triphosphate | ||
| zidovudine triphosphate | |||
| illimaquinone | illimaquinone: structure given in first source; isolated from the Red Sea sponge Smenospongia; inhibits the RNase H. activity of HIV-1 reverse transcriptase | monohydroxy-1,4-benzoquinones; prenylquinone | metabolite |
| sitosterol, (3beta)-isomer | sitosterol : A member of the class of phytosterols that is stigmast-5-ene substituted by a beta-hydroxy group at position 3. Sobatum: tradename; active fraction of Solanum trilobatum; reduces side-effects of radiation-induced toxicity | 3beta-hydroxy-Delta(5)-steroid; 3beta-sterol; C29-steroid; phytosterols; stigmastane sterol | anticholesteremic drug; antioxidant; mouse metabolite; plant metabolite; sterol methyltransferase inhibitor |
| TTP | pyrimidine ribonucleoside 5'-triphosphate | ||
| aphidicolin | aphidicolin : A tetracyclic diterpenoid that has an tetradecahydro-8,11a-methanocyclohepta[a]naphthalene skeleton with two hydroxymethyl substituents at positions 4 and 9, two methyl substituents at positions 4 and 11b and two hydroxy substituents at positions 3 and 9. An antibiotic with antiviral and antimitotical properties. Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication. Aphidicolin: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells. | tetracyclic diterpenoid | antimicrobial agent; antimitotic; antineoplastic agent; antiviral drug; apoptosis inducer; Aspergillus metabolite; DNA synthesis inhibitor; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor; fungal metabolite |
| stigmasterol | stigmasta-5,22-dien-3-ol: isolated from freeze-dried powder of Blackberries (Rubus ursinus L.) which showed an activity on inhibition of chemocarcinogen stigmasterol : A 3beta-sterol that consists of 3beta-hydroxystigmastane having double bonds at the 5,6- and 22,23-positions. | 3beta-hydroxy-Delta(5)-steroid; 3beta-sterol; phytosterols; stigmastane sterol | plant metabolite |
| lyoniside | daucosterol : A steroid saponin that is sitosterol attached to a beta-D-glucopyranosyl residue at position 3 via a glycosidic linkage. It has bee isolated from Panax japonicus var. major and Breynia fruticosa. | beta-D-glucoside; monosaccharide derivative; steroid saponin | plant metabolite |
| corosolic acid | triterpenoid | metabolite | |
| gentamicin sulfate | |||
| edgeworin | edgeworin: from Dirca occidentalis Gray; structure given in first source | ||
| raltegravir | 1,2,4-oxadiazole; dicarboxylic acid amide; hydroxypyrimidine; monofluorobenzenes; pyrimidone; secondary carboxamide | antiviral drug; HIV-1 integrase inhibitor | |
| GS-443902 | GS-441524 triphosphate: intracellular active metabolite of remdesivir GS-443902 : An organic triphosphate that is GS-441524 in which the 5'-hydroxy group has been replaced by a triphosphate group. It is the active metabolite of remdesivir. | aromatic amine; C-nucleoside; nitrile; organic triphosphate; pyrrolotriazine | anticoronaviral agent; antiviral drug; drug metabolite |
| PF-06446846 | PF-06446846 : A triazolopyridine that is 3H-[1,2,3]triazolo[4,5-b]pyridine substituted by a 4-{(3-chloropyridin-2-yl)[(3R)-piperidin-3-yl]carbamoyl}phenyl group at position 3. It is a potent inhibitor of PCSK9. PF-06446846: inhibits translation of PCSK9 ;structure in first source | benzamides; monochloropyridine; piperidines; tertiary carboxamide; triazolopyridine | antilipemic drug; EC 3.4.21.61 (kexin) inhibitor |