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
Guan, Yue
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https://hdl.handle.net/2142/21483
Description
Title
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
Author(s)
Guan, Yue
Issue Date
1994
Director of Research (if dissertation) or Advisor (if thesis)
Wang, Andrew H.J.
Doctoral Committee Chair(s)
Wang, Andrew H.J.
Committee Member(s)
Wraight, Colin A.
Churchill, Mair
Department of Study
Center for Biophysics and Computational Biology
Health Sciences, Pharmacy
Discipline
Biophysics
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Molecular
Chemistry, Pharmaceutical
Health Sciences, Pharmacy
Biophysics, Medical
Health Sciences, Oncology
Language
eng
Abstract
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 $\beta$-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.
Several drug molecules such as ecteinascidins and UK63052, are potent anticancer drugs. The high resolution crystal structural analyses as well as the modeling studies of these molecules provide us with valuable information on how these molecules exert their functions in the living cells. Cyclic ribodiguanylic acid, c-(GpGp), is the endogenous effector regulator of cellulose synthase. Their structural analyses help us in understanding the structure-function relationship of cyclic-DNA/RNAs.
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