PDBsum entry 4rt2

Transferase/DNA

PDB id: 4rt2

Contents

Protein chain

326 a.a.

DNA/RNA

Ligands

N6T

Metals

_MG

_NA ×3

_CL

Waters ×387

PDB id:

4rt2

Name:

Transferase/DNA

Title:

Ternary complex crystal structure of DNA polymerase beta with (alpha, beta)-ch2-(beta,gamma)-nh-dttp

Structure:

DNA polymerase beta. Chain: a. Engineered: yes. DNA (5'-d( Cp Cp Gp Ap Cp Ap Gp Cp Gp Cp Ap Tp Cp Ap Gp C)- 3'). Chain: t. Synonym: template strand. Engineered: yes. DNA (5'-d( Gp Cp Tp Gp Ap Tp Gp Cp Gp (Doc))-3').

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: polb. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic construct. Organism_taxid: 32630.

Resolution:

1.92Å R-factor: 0.179 R-free: 0.211

Authors:

V.K.Batra,S.H.Wilson

Key ref:

A.P.Kadina et al. (2015). Two Scaffolds from Two Flips: (α,β)/(β,γ) CH2/NH "Met-Im" Analogues of dTTP. Org Lett, 17, 2586-2589. PubMed id: 25970636 DOI: 10.1021/acs.orglett.5b00799

Date:

12-Nov-14 Release date: 01-Jul-15

Protein chain

P06746  (DPOLB_HUMAN) -  DNA polymerase beta from Homo sapiens

Seq: 335 a.a.

Struc: 326 a.a.

DNA/RNA chains

C-C-G-A-C-A-G-C-G-C-A-T-C-A-G-C 16 bases

G-C-T-G-A-T-G-C-G-DOC 10 bases

G-T-C-G-G 5 bases

Enzyme reactions

• Enzyme class 1: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 2: E.C.4.2.99.- - ?????
• Enzyme class 3: E.C.4.2.99.18 - DNA-(apurinic or apyrimidinic site) lyase.
• Reaction: 2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)- 2'-deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3- dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-phospho- 2'-deoxyribonucleoside-DNA + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1021/acs.orglett.5b00799

Org Lett 17:2586-2589 (2015)

PubMed id: 25970636

Two Scaffolds from Two Flips: (α,β)/(β,γ) CH2/NH "Met-Im" Analogues of dTTP.

A.P.Kadina, B.A.Kashemirov, K.Oertell, V.K.Batra, S.H.Wilson, M.F.Goodman, C.E.McKenna.

ABSTRACT

Novel α,β-CH2 and β,γ-NH (1a) or α,β-NH and β,γ-CH2 (1b) "Met-Im" dTTPs were synthesized via monodemethylation of triethyl-dimethyl phosphorimido-bisphosphonate synthons (4a, 4b), formed via a base-induced [1,3]-rearrangement of precursors (3a, 3b) in a reaction with dimethyl or diethyl phosphochloridate. Anomerization during final bromotrimethylsilane (BTMS) deprotection after Mitsunobu conjugation with dT was avoided by microwave conditions. 1a was 9-fold more potent in inhibiting DNA polymerase β, attributed to an NH-group interaction with R183 in the active site.