PDBsum entry 5b1c

Immune system

PDB id: 5b1c

Contents

Protein chains

97 a.a.

Ligands

SO4 ×5

Waters ×243

PDB id:

5b1c

Name:

Immune system

Title:

Crystal structure of den4 ed3 mutant with l387i

Structure:

Envelope protein e. Chain: b, a, c. Fragment: domain 3, unp residues 575-679. Engineered: yes. Mutation: yes

Source:

Dengue virus 4 dominica/814669/1981. Denv-4. Organism_taxid: 408871. Strain: dominica/814669/1981. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.00Å R-factor: 0.217 R-free: 0.240

Authors:

M.R.Kulkarni,N.Numoto,N.Ito,Y.Kuroda

Key ref:

M.R.Kulkarni et al. (2016). Modeling and experimental assessment of a buried Leu-Ile mutation in dengue envelope domain III. Biochem Biophys Res Commun, 471, 163-168. PubMed id: 26826384 DOI: 10.1016/j.bbrc.2016.01.159

Date:

02-Dec-15 Release date: 24-Feb-16

Protein chains

P09866  (POLG_DEN4D) -  Genome polyprotein from Dengue virus type 4 (strain Dominica/814669/1981)

Seq: 3387 a.a.

Struc: 97 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
• 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⁺
• 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⁺

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.bbrc.2016.01.159

Biochem Biophys Res Commun 471:163-168 (2016)

PubMed id: 26826384

Modeling and experimental assessment of a buried Leu-Ile mutation in dengue envelope domain III.

M.R.Kulkarni, N.Numoto, N.Ito, Y.Kuroda.

ABSTRACT

Envelope protein domain III (ED3) of the dengue virus is important for both antibody binding and host cell interaction. Here, we focused on how a L387I mutation in the protein core could take place in DEN4 ED3, but cannot be accommodated in DEN3 ED3 without destabilizing its structure. To this end, we modeled a DEN4_L387I structure using the Penultimate Rotamer Library and taking the DEN4 ED3 main-chain as a fixed template. We found that three out of seven Ile(387) conformers fit in DEN4 ED3 without introducing the severe atomic clashes that are observed when DEN3 serotype's ED3 is used as a template. A more extensive search using 273 side-chain rotamers of the residues surrounding Ile(387) confirmed this prediction. In order to assess the prediction, we determined the crystal structure of DEN4_L387I at 2 Å resolution. Ile(387) indeed adopted one of the three predicted rotamers. Altogether, this study demonstrates that the effects of single mutations are to a large extent successfully predicted by systematically modeling the side-chain structures of the mutated as well as those of its surrounding residues using fixed main-chain structures and assessing inter-atomic steric clashes. More accurate and reliable predictions require considering sub-angstrom main-chain deformation, which remains a challenging task.