Literature summary for 3.1.99.B1 extracted from

Sgrignani, J.; Magistrato, A.
QM/MM MD simulations on the enzymatic pathway of the human flap endonuclease (hFEN1) elucidating common cleavage pathways to RNase H enzymes (2015), ACS Catal., 5, 3864-3875 .

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Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P39748	-	-

Reaction

Reaction	Comment	Organism	Reaction ID
endonucleases that remove 5' DNA sequences from a DNA structure called a DNA flap. The DNA flap structure occurs in double-stranded DNA containing a single-stranded break where the 5' portion of the downstream strand is too long and overlaps the 3' end of the upstream strand. Flap endonucleases cleave the downstream strand of the overlap flap structure precisely after the first base-paired nucleotide, creating a ligatable nick	in a most likely reaction pathway (very similar to that recently proposed for ribonuclease H, EC 3.1.13.2) the rate-determining step is the SN2-like nucleophilic attack of a water to the scissile phosphate, which occurs concomitantly with its activation by the pro-Rp oxygen of the nucleobase flanking the scissile phosphate. Preactivation of the nucleophilic water. Scheme of different possible reaction mechanisms, overview	Homo sapiens	a

Source Tissue

Source Tissue	Comment	Organism	Textmining
additional information	FEN1 is overexpressed in all proliferative tissues	Homo sapiens	-

Synonyms

Synonyms	Comment	Organism
flap endonuclease	-	Homo sapiens
hFEN1	-	Homo sapiens

General Information

General Information	Comment	Organism
additional information	mixed quantum-classical (QM/MM) metadynamics and umbrella sampling free energy calculations are employed on a reconstructed reactive hFEN/double strand (ds) DNA adduct for an atomistic and energetic rendering of the enzymatic catalysis promoted by the human FEN1, structure-function analysis, overview. The enzymatic phosphate hydrolysis proceeds as an SN2-like nucleophilic attack on the scissile phosphate performed by an hydroxide ion, which is typically formed upon water activation	Homo sapiens
physiological function	Flap endonucleases (FENs) are nucleic acid hydrolyzing enzymes in charge of excising 5'-small DNA and RNA fragments (flaps) protruding from nucleic acid structures during the lagging strand DNA replication or the longpatch base excision repair (LP-BER) processes. Important role of FENs in maintaining nucleic acid fidelity and cell proliferation, high levels of FEN1 are believed to support cancer cell hyperproliferation	Homo sapiens

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Release 2023.1 (January 2023)