PDBsum entry 5eif

Transferase

PDB id: 5eif

Contents

Protein chains

256 a.a.

Ligands

SAM ×2

4M0

Waters ×734

PDB id:

5eif

Name:

Transferase

Title:

Dengue 3 ns5 methyltransferase bound to s-adenosyl methionine and fragment nb2c3

Structure:

Genome polyprotein. Chain: a, c. Ec: 3.4.21.91,3.6.1.15,3.6.4.13,2.1.1.56,2.1.1.57,2.7.7.48. Engineered: yes

Source:

Dengue virus type 3. Denv-3. Organism_taxid: 408870. Strain: philippines/h87/1956. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta.

Resolution:

1.50Å R-factor: 0.163 R-free: 0.188

Authors:

K.Barral,G.Bricogne,A.Sharff

Key ref:

F.Benmansour et al. (2017). Discovery of novel dengue virus NS5 methyltransferase non-nucleoside inhibitors by fragment-based drug design. Eur J Med Chem, 125, 865-880. PubMed id: 27750202 DOI: 10.1016/j.ejmech.2016.10.007

Date:

29-Oct-15 Release date: 26-Oct-16

Protein chains

P27915  (POLG_DEN3P) -  Genome polyprotein from Dengue virus type 3 (strain Philippines/H87/1956)

Seq: 3390 a.a.

Struc: 256 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: E.C.2.1.1.56 - mRNA (guanine-N(7))-methyltransferase.
• Reaction: a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L- methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-homocysteine

5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L- methionine (Bound ligand (Het Group name = SAM) corresponds exactly) = 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-homocysteine

• Enzyme class 2: E.C.2.1.1.57 - methyltransferase cap1.
• Reaction: a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)- (2'-O-methyl-ribonucleoside) in mRNA + S-adenosyl-L-homocysteine + H⁺

5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine (Bound ligand (Het Group name = SAM) corresponds exactly) = 5'-end (N(7)-methyl 5'-triphosphoguanosine)- (2'-O-methyl-ribonucleoside) in mRNA + S-adenosyl-L-homocysteine + H(+)

• Enzyme class 3: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
• Enzyme class 4: E.C.3.4.21.91 - flavivirin.
• Reaction: Selective hydrolysis of Xaa-Xaa-|-Xbb bonds in which each of the Xaa can be either Arg or Lys and Xbb can be either Ser or Ala.
• Enzyme class 5: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.
• Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺
• Enzyme class 6: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

ATP + H2O = ADP (Bound ligand (Het Group name = SAM) matches with 50.00% similarity) + phosphate + 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

reference

DOI no: 10.1016/j.ejmech.2016.10.007

Eur J Med Chem 125:865-880 (2017)

PubMed id: 27750202

Discovery of novel dengue virus NS5 methyltransferase non-nucleoside inhibitors by fragment-based drug design.

F.Benmansour, I.Trist, B.Coutard, E.Decroly, G.Querat, A.Brancale, K.Barral.

ABSTRACT

No abstract given.