摘要:
This invention provides fragments of HCV NS3 helicase, and crystalline compositions thereof, based on subdomains of HCV helicase protein. The protein fragments are stable, soluble, and structurally sound. They can be expressed at high levels in conventional expressions systems, such as E. coli, to permit efficient, large-scale production for NMR-based screening applications and production of [2H,13C,15N]- and [13C,15N]-labeled polypeptides for structural NMR studies. Helicase fragments of the present invention are useful in the most advanced NMR techniques available, e.g., NMR-based drug discovery techniques such as SAR-by-NMR, in biological assays to discover inhibitors of HCV NS3 helicase, and to evaluate the mechanism of action and substrates for HCV NS3 helicase. Crystals of the present invention are useful for structure-based drug design studies using x-ray crystallographic techniques.
摘要:
The invention relates to the purification and crystallization of hepatitis C virus (HCV) NS3/NS4A polypeptide complex. Also, crystallization conditions for NS3/NS4A are provided. Further, the atomic coordinates for the NS3/NS4A protein are disclosed. Examples of its use for the determination of the three-dimensional atomic structures of HCV NS3/NS4A with substrate(s) or substrate analog(s) or inhibitor complexes are also provided.
摘要:
The present invention discloses nucleic acids that encode an active human Aurora 2 kinase catalytic domain. The present invention also discloses methods of growing X-ray diffractable crystals of polypeptides comprising the active human Aurora 2 kinase catalytic domain. The present invention further discloses a crystalline form of a catalytic domain of human Aurora 2 kinase. In addition, the present invention discloses methods of using the X-ray diffractable crystals of human Aurora 2 kinase in structure assisted drug design to identify compounds that can modulate the enzymatic activity of human Aurora 2 kinase.
摘要:
The present invention discloses purified polypeptides that comprise an active human ADAM33 catalytic domain. In addition, the present invention discloses nucleic acids that encode the polypeptides of the present invention. The present invention also discloses methods of growing X-ray diffractable crystals of polypeptides comprising the active human ADAM33 catalytic domain. The present invention further discloses a crystalline form of a catalytic domain of human ADAM33. In addition, the present invention discloses methods of using the X-ray diffractable crystals of human ADAM33 in structure based drug design to identify compounds that can modulate the enzymatic activity of human ADAM33. The present invention also discloses methods of treating respiratory disorders by administering therapeutic amounts of the human ADAMS33 catalytic domain.
摘要:
The present invention provides, in part, AKT3 polypeptides and methods of use thereof along with nucleic acids encoding the polypeptides. For example, methods for screening for AKT3 inhibitors are provided herein.
摘要:
The present invention discloses modified Hdm2 proteins that are soluble. In addition, the present invention discloses nucleic acids that encode the modified Hdm2 proteins of the present invention. The invention also provides crystals of modified Hdm2 proteins that are suitable for X-ray crystallization analysis. The present invention also discloses methods of using the modified Hdm2 proteins and crystals thereof to identify, select and/or design compounds that may be used as anticancer agents. The present invention further discloses compounds that bind to modified Hdm2 proteins in protein-ligand complexes.
摘要:
The present invention discloses modified Hdm2 proteins that are soluble. In addition, the present invention discloses nucleic acids that encode the modified Hdm2 proteins of the present invention. The invention also provides crystals of modified Hdm2 proteins that are suitable for X-ray crystallization analysis. The present invention also discloses methods of using the modified Hdm2 proteins and crystals thereof to identify, select and/or design compounds that may be used as anticancer agents. The present invention further discloses compounds that bind to modified Hdm2 proteins in protein-ligand complexes.