PDBsum entry 3fsi

Transferase/DNA

PDB id: 3fsi

Contents

Protein chain

248 a.a. *

DNA/RNA

Ligands

ACT ×5

MWB

Waters ×228

* Residue conservation analysis

PDB id:

3fsi

Name:

Transferase/DNA

Title:

Crystal structure of a trypanocidal 4,4'-bis(imidazolinylamino) diphenylamine bound to DNA

Structure:

Reverse transcriptase domain. Chain: a. Fragment: reverse transcriptase domain: unp residues 144-398. Synonym: rt. Engineered: yes. 5'-d( Cp Tp Tp Ap Ap Tp Tp C)-3'. Chain: g. Engineered: yes. 5'-d(p Gp Ap Ap Tp Tp Ap Ap G)-3'.

Source:

Moloney murine leukemia virus. Virus. Organism_taxid: 11801. Gene: momlv, pol. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic: yes

Resolution:

1.75Å R-factor: 0.231 R-free: 0.254

Authors:

L.S.Glass,M.M.Georgiadis,K.D.Goodwin

Key ref:

L.S.Glass et al. (2009). Crystal structure of a trypanocidal 4,4'-bis(imidazolinylamino)diphenylamine bound to DNA. Biochemistry, 48, 5943-5952. PubMed id: 19405506

Date:

09-Jan-09 Release date: 19-May-09

Protein chain

P03355  (POL_MLVMS) -  Gag-Pol polyprotein from Moloney murine leukemia virus (isolate Shinnick)

Seq: 1738 a.a.

Struc: 248 a.a.

DNA/RNA chains

C-T-T-A-A-T-T-C 8 bases

G-A-A-T-T-A-A-G 8 bases

Enzyme reactions

• Enzyme class 2: E.C.2.7.7.- - ?????
• Enzyme class 3: E.C.2.7.7.49 - RNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 4: E.C.2.7.7.7 - DNA-directed Dna polymerase.
• Reaction: DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphate
• Enzyme class 5: E.C.3.1.-.-
• Enzyme class 6: E.C.3.1.26.4 - ribonuclease H.
• Reaction: Endonucleolytic cleavage to 5'-phosphomonoester.
• Enzyme class 7: E.C.3.4.23.- - ?????

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

Biochemistry 48:5943-5952 (2009)

PubMed id: 19405506

Crystal structure of a trypanocidal 4,4'-bis(imidazolinylamino)diphenylamine bound to DNA.

L.S.Glass, B.Nguyen, K.D.Goodwin, C.Dardonville, W.D.Wilson, E.C.Long, M.M.Georgiadis.

ABSTRACT

The pursuit of small molecules that bind to DNA has led to the discovery of selective and potent antitrypanosomal agents, specifically 4,4'-bis(imidazolinylamino)- and 4,4'-bis(guanidino)diphenylamine compounds, CD27 and CD25, respectively. Although the antitrypanosomal properties of these compounds have been characterized, further development of this series of compounds requires assessment of their DNA site selectivities and affinities. Toward this end, both compounds have been analyzed and found to selectively bind AT sequences. However, CD27 was found to bind with higher affinity to 5'-AATT than 5'-ATAT while CD25 bound more weakly but equally well to either sequence. To detail the nature of its interactions with DNA, the crystal structure of CD27, bound to its preferred DNA-binding site 5'-AATT within a self-complementary oligonucleotide, 5'-d(CTTAATTCGAATTAAG), was determined at 1.75 A using a host-guest approach. Although CD27 is predicted to be highly twisted in its energy-minimized state, it adopts a more planar crescent shape when bound in the minor groove of the DNA. Interactions of CD27 with 5'-AATT include bifurcated hydrogen bonds, providing a basis for selectivity of this site, and favorable van der Waals interactions in a slightly widened minor groove. Thus, an induced fit results from conformational changes in both the ligand and the DNA. Our studies suggest a basis for understanding the mechanism of the antitrypanosomal activity of these symmetric diphenylamine compounds.