1. X-ray crystallographic analyses of the gene V protein from Ff bacteriophage, a single-stranded DNA-binding protein, and its Y41 mutants 2. X-ray crystallographic analyses of several anticancer drugs and their interactions with DNA

In biological systems, DNA/RNA-protein interactions as well as drug-DNA interactions play important roles in genetic processes. A fundamental understanding of these processes requires a detailed structural knowledge of DNAs, proteins, drugs, as well as their complexes with each other. Gene V protein (GVP) encoded by the filamentous bacteriophage Ff (M13, f1, fd) is a single-stranded DNA (ssDNA) binding protein which binds to ssDNA non-specifically and cooperatively. The structure of the wild-type protein has been determined and refined at 1.8A resolution (Skinner et al., (1994) Proc. Natl. Acad. Sci. USA. 91, 2071-2075). It is largely composed of β-structure with three prominent loops: DNA-binding loop, dyad loop and dimer contact loop. Y41 plays an essential role in the dimer-dimer interactions of the protein-ssDNA complex. Two Y41 mutant structures, namely Y41F and Y41H, have been studied by X-ray crystallography to high resolution. Y41F GVP crystallized isomorphously to the wild-type, while Y41H GVP crystallized in a different space group (P2$\sb12\sb12\sb1).$ Y41H GVP structure has been solved by the molecular replacement method. In both crystals, the loop (residues 36-43) that contains residue 41 is involved in the crystal dimer packings, but in a different manner. Using the crystal packing infomations as guidance, we were able to construct the GVP-ssDNA complex model, consistent with existing biochemical and biophysical data.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Guan, Yue

Contributors dc:contributor

• Wang, Andrew H.J.
• Wraight, Colin A.
• Churchill, Mair

• Biology, Molecular
• Chemistry, Pharmaceutical
• Health Sciences, Pharmacy
• Biophysics, Medical
• Health Sciences, Oncology

Statement dc:rights

• Copyright 1994 Yue Guan

Language dc:language

eng

Identifier

AAI9512380
(UMI)AAI9512380

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/21483