Protein crystallographic studies on rubredoxin and contortrostatin

The present dissertation work is devoted to the protein crystallographic studies on two small proteins, rubredoxin and contortrostatin.; The first part of the thesis describes neutron crystallographic studies on wild-type rubredoxin from highly hyperthermophilic bacteria Pyrococcus furiosus. This neutron study was motivated by the hope that more accurate parameters of hydrogen and deuterium positions and hydrogen bonds obtained using neutron diffraction method can help in explaining the unusually high thermostability of wild-type rubredoxin. This part of work was based on the previously known X-ray structure of the wild-type rubredoxin from Pyrococcus furiosus. The first chapter of this thesis is a brief introduction to the rubredoxins and their properties, including thermostability. The fourth chapter of the thesis gives details of the neutron structure determination of wild-type rubredoxin from Pyrococcus furiosus.; The third chapter of this dissertation gives details of crystallization methods used for obtaining diffraction quality crystals for both proteins.; The second part of the thesis describes synchrotron X-ray studies on relatively novel protein, contortrostatin from Agkistrodon contortrix contortrix. One most important property of contortrostatin is the ability to inhibit the growth of cancer cell via disruption of integrin-cell interactions (i.e., the interference with the adhesion properties of tumor cells). The present X-ray structure determination was initiated in the hope that details of the three-dimensional structure can help in understanding the molecular basis of action of this interesting protein. The second chapter of the dissertation is an introduction to the disintegrins, the family of small polypeptides, including contortrostatin, and their properties. The fifth chapter of the thesis gives details of the current progress being made in the X-ray crystal structure determination of contortrostatin, especially in applying the multiple anomalous dispersion (MAD) method to solve its structure. Substantial progress has been made in the crystal structure determination of this important molecule, and the full three-dimensional structure of this protein will be available shortly.