Student Projects for UMass Chemistry 423 Spring 2011: Difference between revisions
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<StructureSection load='1wat' size='400' side='right' scene='User:Lynmarie_K_Thompson/Sandbox_1/Loadedfrompdb/4' caption=''> | |||
Instructions and signup page (1-6 below) were posted in Sandbox423 for all students to edit. Students created projects (7-8 below, and additional links in section 3) on separate sandbox pages. | |||
''' Spring 2011 Chem423 Team Projects: Understanding Drug Mechanisms''' | ''' Spring 2011 Chem423 Team Projects: Understanding Drug Mechanisms''' | ||
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{{Clear}} | {{Clear}} | ||
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[[UMass Chem 423 Student Projects 2011-1]] | [[UMass Chem 423 Student Projects 2011-1]]: | ||
Wednesday 4/27/11 | Wednesday 4/27/11 | ||
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Varun Chalupadi, Anthony Laviola, Tiffany Brucker, Alan Stebbins - Cyclooxygenase | Varun Chalupadi, Anthony Laviola, Tiffany Brucker, Alan Stebbins - Cyclooxygenase | ||
[[UMass Chem 423 Student Projects 2011-2]] | [[UMass Chem 423 Student Projects 2011-2]]: | ||
Inna Brockman, Robert Nathan, Sarena Horava, Nick Cadirov - p38 kinase | Inna Brockman, Robert Nathan, Sarena Horava, Nick Cadirov - p38 kinase | ||
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=='''Flu Neuraminidase'''== | =='''Flu Neuraminidase'''== | ||
[[Image:neuraminidase-and-tamiflu.jpg| | [[Image:neuraminidase-and-tamiflu.jpg|left|300px]]<br /> | ||
{{clear}} | |||
===Introduction=== | ===Introduction=== | ||
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===Overall Structure=== | ===Overall Structure=== | ||
Influenza (flu) Neuraminidase is a homotetramer, with four identical subunits. Each subunit consists mostly of antiparallel beta sheets and three alpha helices, with a beta-propeller folding pattern (<scene name='Sandbox45/Secondary_structure/2'>Secondary Structure</scene>). | Influenza (flu) Neuraminidase is a homotetramer, with four identical subunits. Each subunit consists mostly of antiparallel beta sheets and three alpha helices, with a beta-propeller folding pattern (<scene name='Sandbox45/Secondary_structure/2'>Secondary Structure</scene>). | ||
As shown, the alpha helices lie toward the center of the protein. | As shown, the alpha helices lie toward the center of the protein. | ||
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===Additional Features=== | ===Additional Features=== | ||
Neuraminidase breaks the <scene name='Sandbox45/Sialic_acid_and_neuraminidase/1'>sialic acid</scene> groups from glycoproteins. <scene name='Sandbox45/Sialic_acid_and_hemagglutinin/1'>Hemagglutinin</scene> from on the virus attaches to the sialic acid groups. The virus is from the cell and is released when neuraminidase breaks the sialic acid groups. This will allow flu replication to happen and a neuraminidase inhibitor, such as Tamiflu, is required to stop neuraminidase. The interaction of Tamiflu with N1 neuraminidase is shown with this <scene name='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/Morph_2hty_to_2hu4/8'>morph</scene> (1). Tamiflu in this model is bound when it is visible and the loop in moved in towards the drug through induced fit. | Neuraminidase breaks the <scene name='Sandbox45/Sialic_acid_and_neuraminidase/1'>sialic acid</scene> groups from glycoproteins. <scene name='Sandbox45/Sialic_acid_and_hemagglutinin/1'>Hemagglutinin</scene> from on the virus attaches to the sialic acid groups. The virus is from the cell and is released when neuraminidase breaks the sialic acid groups. This will allow flu replication to happen and a neuraminidase inhibitor, such as Tamiflu, is required to stop neuraminidase. The interaction of Tamiflu with N1 neuraminidase is shown with this <scene name='Avian_Influenza_Neuraminidase,_Tamiflu_and_Relenza/Morph_2hty_to_2hu4/8'>morph</scene> (1). Tamiflu in this model is bound when it is visible and the loop in moved in towards the drug through induced fit. | ||
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=='''Influenza M2 Proton Channel'''== | =='''Influenza M2 Proton Channel'''== | ||
===Introduction=== | ===Introduction=== | ||
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Influenza A, better known as the flu, an infection of the nose, throat, and lungs caused by the influenza virus. Basic symptoms include aches, chills, fever, loss of energy and dizziness, but complications can include pneumonia, encephalitis, bronchitis, and death—about 36,000 people every year die of complications from the flu (CDC). | Influenza A, better known as the flu, an infection of the nose, throat, and lungs caused by the influenza virus. Basic symptoms include aches, chills, fever, loss of energy and dizziness, but complications can include pneumonia, encephalitis, bronchitis, and death—about 36,000 people every year die of complications from the flu (CDC). | ||
The M2 protein is a proton-selective ion channel protein that plays an important role in the life cycle of the influenza A virus. The channel itself is a homotetramer with four identical M2 units, where each M2 protein is a helix stabilized by two disulfide bonds. At a low pH, the channel allows hydrogen ions to enter the viral particle form the endosome, effectively lowering the pH on the interior of the virus. This in turn causes the dissociation of the viral matrix protein M1 from the ribonucleoprotein, a critical step in “uncoating” the virus to introduce its contents to the cytoplasm of the host cell (Stouffer). The M2 protein itself consists of three major protein domains: a stretch of 24 amino acids on the N-terminal end that are exposed to the external environment, 22 (largely hydrophobic) amino acids in the transmembrane region, and 52 amino acids on the C-terminal end which are exposed to the inside of the viral particle (Schnell). | The <scene name='Student_Projects_for_UMass_Chemistry_423_Spring_2011/Cv/1'>M2 protein is a proton-selective ion channel protein </scene> that plays an important role in the life cycle of the influenza A virus. The channel itself is a homotetramer with four identical M2 units, where each M2 protein is a helix stabilized by two disulfide bonds. At a low pH, the channel allows hydrogen ions to enter the viral particle form the endosome, effectively lowering the pH on the interior of the virus. This in turn causes the dissociation of the viral matrix protein M1 from the ribonucleoprotein, a critical step in “uncoating” the virus to introduce its contents to the cytoplasm of the host cell (Stouffer). The M2 protein itself consists of three major protein domains: a stretch of 24 amino acids on the N-terminal end that are exposed to the external environment, 22 (largely hydrophobic) amino acids in the transmembrane region, and 52 amino acids on the C-terminal end which are exposed to the inside of the viral particle (Schnell). | ||
The function of the M2 channel can be inhibited by the antiviral drug Amantadine, an inhibition that effectively blocks the virus from taking over the host cell. Amantadine inhibits the replication of influenza A viruses by interfering with the uncoating of the virus within the cell. Amantadine is an M2 inhibitor that blocks the ion channel formed by the M2 protein that spans the viral membrane. By blocking this channel, Amantadine effectively prevents the acidification and subsequent release of viral elements into the host cell. Unfortunately, the M2 gene is susceptible to mutations. When one of five (of the 22) amino acids in the transmembrane region is suitably substituted, Amantadine no longer binds in such a way that would block the motion of the protons into the virus. As of 2009, the CDC noted that a full 100% of Influenza A viruses of types H3N2 and 2009 pandemic flu samples cultured in the United States showed a resistance to Amantadine (CDC). | The function of the M2 channel can be inhibited by the antiviral drug Amantadine, an inhibition that effectively blocks the virus from taking over the host cell. Amantadine inhibits the replication of influenza A viruses by interfering with the uncoating of the virus within the cell. Amantadine is an M2 inhibitor that blocks the ion channel formed by the M2 protein that spans the viral membrane. By blocking this channel, Amantadine effectively prevents the acidification and subsequent release of viral elements into the host cell. Unfortunately, the M2 gene is susceptible to mutations. When one of five (of the 22) amino acids in the transmembrane region is suitably substituted, Amantadine no longer binds in such a way that would block the motion of the protons into the virus. As of 2009, the CDC noted that a full 100% of Influenza A viruses of types H3N2 and 2009 pandemic flu samples cultured in the United States showed a resistance to Amantadine (CDC). | ||
