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Friday, March 12, 2010
Thursday, March 11, 2010
Find a protein using PDB explorer, describe you protein including disease state or real world application it has.
* Find a protein using PDB explorer, describe you protein including disease state or real world application it has.
When looking to perform research on proteins, one finds that there are many entry level sites available for free on the web. I have linked a couple of the sites below. I have chosen to find and report HIV protease. This is a key enzyme contributing to the overall virulence factor of HIV/AIDS. I recently, March 4th do be exact presented a PowerPoint presentation. The presentation happened to be on targeting proteins, more specifically enzymes in the treatment of HIV. I have placed a link to the presentation below. I hope that this presentation can answer the question of how a protein can related to a disease and more importantly, how can targeting that proteins function impact the virulence of the disease.
Specifically, when the new virus buds off from the host cell, it achieves maturation
by HIV protease cleaving the longs budding strands into fragments of smaller size. These smaller fragments are the functional strands which are packaged into other viral components in order to create a new virus.
into smaller functional fragments by HIV proteases
PowerPoint presentation on HIV/AIDS, March 4th, 2010.
HIV/AIDS ENZYME TREATMENT
Protein Database Site:
MCSG Goverment Site
Additional Protein Site:
www.RCSB.org
___________________________________________________________
Protein of interest:
HIV Protease (Quaternary Structure)
HIV Protease
_______________________________________
Protease inhibitors (PIs) are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new virons.
Protease inhibitors have been developed or are presently undergoing testing for treating various viruses:
About Wikepedia and Pasting:
________________________________________________________
When you paste from Wikipedia, please note that the information can be just plain wrong. But it contains some much information that is both accessible and easy to use. When you paste a paragraph, often the links paste with it, giving you the links back to the site. This is self serving and can be a distraction to your site, due to the fact that you navigate away from your site, but it can be a great way of presenting NON-FACT CHECKED INFORMATION easily and without a ton of effort on your part.
ENJOY READING THE REMAINDER OF THE BLOG ENTRIES BELOW.
MCB
Signing Off :-)
___________________________________________________________
When looking to perform research on proteins, one finds that there are many entry level sites available for free on the web. I have linked a couple of the sites below. I have chosen to find and report HIV protease. This is a key enzyme contributing to the overall virulence factor of HIV/AIDS. I recently, March 4th do be exact presented a PowerPoint presentation. The presentation happened to be on targeting proteins, more specifically enzymes in the treatment of HIV. I have placed a link to the presentation below. I hope that this presentation can answer the question of how a protein can related to a disease and more importantly, how can targeting that proteins function impact the virulence of the disease.
Specifically, when the new virus buds off from the host cell, it achieves maturation
by HIV protease cleaving the longs budding strands into fragments of smaller size. These smaller fragments are the functional strands which are packaged into other viral components in order to create a new virus.
into smaller functional fragments by HIV proteases
PowerPoint presentation on HIV/AIDS, March 4th, 2010.
HIV/AIDS ENZYME TREATMENT
Protein Database Site:
MCSG Goverment Site
Additional Protein Site:
www.RCSB.org
___________________________________________________________
Protein of interest:
HIV Protease (Quaternary Structure)
HIV Protease
HIV Protease from the RCSB site pasted below:
Fragment-Based Screen against HIV Protease
Perryman, A.P., Zhang, Q., Soutter, H.H., Rosenfeld, R., McRee, D.E., Olson, A.J., Elder, J.E., Stout, C.D.
(2010) Chem.Biol.Drug Des. 75: 257-268
Perryman, A.P., Zhang, Q., Soutter, H.H., Rosenfeld, R., McRee, D.E., Olson, A.J., Elder, J.E., Stout, C.D.
(2010) Chem.Biol.Drug Des. 75: 257-268
Source Hide Polymer: 1 Scientific Name: Human immunodeficiency virus 1 
Expression System: Escherichia coli
Related PDB Entries Hide Id Details 2AZ8 HIV-1 PROTEASE NL4-3 IN COMPLEX WITH INHIBITOR, TL-3, WILD TYPE 2AZ9 HIV-1 PROTEASE NL4-3 IN COMPLEX WITH INHIBITOR, TL-3, 1X MUTANT 2AZB HIV-1 PROTEASE NL4-3 IN COMPLEX WITH INHIBITOR, TL-3, 3X MUTANT 2AZC HIV-1 PROTEASE NL4-3 IN COMPLEX WITH INHIBITOR, TL-3, 6X MUTANT 3KF1 HIV Protease (PR) dimer without inhibitor; acetate in exo site 3KFN HIV Protease (PR) with inhibitor TL-3 and fragment hit 4D9 by soaking 3KFP HIV Protease (PR) with inhibitor TL-3 bound, and DMSOs in exo site 3KFR HIV Protease (PR) dimer with inhibitor TL-3 bound and fragment 1F1 in the outside/top of flap 3KFS HIV Protease (PR) dimer with inhibitor TL-3 bound and fragment 2F4 in the outside/top of flap
The above information is a sample of the type of information one can find while visiting a a protein database site. The information can be kind of overwhelming, but this is the nature of current molecular research today. It will probably only get more detailed from here, in the future.
______________________________________________
General Information about Protease inhibitors Pasted Below from Wikipedia:
Protease inhibitor (pharmacology)
From Wikipedia, the free encyclopedia:
Protease inhibitors (PIs) are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new virons.
Protease inhibitors have been developed or are presently undergoing testing for treating various viruses:
- HIV/AIDS: antiretroviral protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir, amprenavir[1] etc.)
- Hepatitis C: experimental agents: BILN 2061 (All clinical trials of BILN 2061 have been suspended due to cardiac issues), VX 950 (trade name Telaprevir), or SCH 503034[2]
About Wikepedia and Pasting:
________________________________________________________
When you paste from Wikipedia, please note that the information can be just plain wrong. But it contains some much information that is both accessible and easy to use. When you paste a paragraph, often the links paste with it, giving you the links back to the site. This is self serving and can be a distraction to your site, due to the fact that you navigate away from your site, but it can be a great way of presenting NON-FACT CHECKED INFORMATION easily and without a ton of effort on your part.
ENJOY READING THE REMAINDER OF THE BLOG ENTRIES BELOW.
MCB
Signing Off :-)
___________________________________________________________
Friday, March 5, 2010
Responce to the Questions asked by class mates about March 4th, 2010, Pesentation on: Treatment fo AIDS by Enzymatic Targets.
On March 4th I gave a 5 minute presentation on: The Treatment of AIDS. The class was kind enough to post some questions after the presentation was finished. I have looked up possible answers to the questions asked.
PLEASE NOTE THAT THE PowerPoint IS LINKED ABOVE IN PROTEIN BLOG.
The following passages are written in response to the questions asked and my results found pertaining to them:
Please note: I am no authority on this subject and if anybody has another view, please post a comment to the blog. I wish for this blog not only to be accurate, but to be representative of a variety of viewpoints.
* HIV is the beginning and AIDS is actively replicating disease phase?
Yes, I reversed these two distinctions during the presentation.
* Are the cells called CD 4 or is that another aspect?
That is another aspect, they are commonly referred to as CD 4, but that is an antigen they carry, not the cell itself the immune cell commonly called the Helper T cell would be more accurate.
"It turns out that CD4 isn't enough. Another protein called CCR5 is needed as well. CCR5, called a co-receptor because it works with CD4, is the door that opens to allow HIV to enter the cell." Stanford School of Medicine Blog:
http://www.thetech.org/genetics/news.php?id=13
* Is AIDS transmitted to Offspring Via the mother?
AIDS can cross the placental barrier, but not always.
AIDS does not appear to be readily passed to offspring genetically.
"If a pro-virus has been integrated into germ-line cells (eggs or sperm), it is passed on to the following generation (the offspring). This process has been occurring for many thousands of years in humans and these retro-viral sequences now account for approximately 8% of the human genome!"
http://www.biotrends.org/science_society/science_society_Science_Basics_HIVAIDS.htm
Targeted Cells:
The virus, entering through which various routes, act primarily on the following cells:
* Lymphoreticular system:
o CD4+ T-Helper cells
o Macrophages
o Monocytes
o B-lymphocytes
* Certain endothelial cells
* Central nervous system:
o Microglia of the nervous system
o Astrocytes
o Oligodendrocytes
o Neurones – indirectly by the action of cytokines and the gp-120
Source: The Wikipedia site had the above list of affected somatic cells.
Note: the gametic cells, responsible for sexual reproduction are not on the list.
* What are the treatments for AIDS?
HAART, or Highly Active Anti-retro viral Therapy is a cocktail taken multiple times per day by aids patients. This is the new front line medication for HIV/AIDS. This chemotherapy can halt the progression of the disease dramatically.
http://www.healthscout.com/ency/68/101/main.html
* Had I heard of a patient who is clear of HIV for 2 years post bone marrow transplant?
Yes, I believe that I had heard of a person in Germany who was immune and they did a graft to try and get the immune cells to multiply.
Wikipedia had this to say about the German patient:
"In Berlin, Germany, a 42-year-old leukemia patient infected with HIV for more than a decade was given an experimental transplant of bone marrow with cells that contained an unusual natural variant of the CCR5 cell-surface receptor. This CCR5-Δ32 variant has been shown to make some cells from people who are born with it resistant to infection with some strains of HIV. Almost two years after the transplant, and even after the patient reportedly stopped taking anti-retro viral medications, HIV has not been detected in the patient's blood.[126]"
Thanks again to my fellow students for your questions and especially for your corrections.
I look forward to the rest of the presentations!!!
MCB
PLEASE NOTE THAT THE PowerPoint IS LINKED ABOVE IN PROTEIN BLOG.
The following passages are written in response to the questions asked and my results found pertaining to them:
Please note: I am no authority on this subject and if anybody has another view, please post a comment to the blog. I wish for this blog not only to be accurate, but to be representative of a variety of viewpoints.
* HIV is the beginning and AIDS is actively replicating disease phase?
Yes, I reversed these two distinctions during the presentation.
* Are the cells called CD 4 or is that another aspect?
That is another aspect, they are commonly referred to as CD 4, but that is an antigen they carry, not the cell itself the immune cell commonly called the Helper T cell would be more accurate.
"It turns out that CD4 isn't enough. Another protein called CCR5 is needed as well. CCR5, called a co-receptor because it works with CD4, is the door that opens to allow HIV to enter the cell." Stanford School of Medicine Blog:
http://www.thetech.org/genetics/news.php?id=13
* Is AIDS transmitted to Offspring Via the mother?
AIDS can cross the placental barrier, but not always.
AIDS does not appear to be readily passed to offspring genetically.
"If a pro-virus has been integrated into germ-line cells (eggs or sperm), it is passed on to the following generation (the offspring). This process has been occurring for many thousands of years in humans and these retro-viral sequences now account for approximately 8% of the human genome!"
http://www.biotrends.org/science_society/science_society_Science_Basics_HIVAIDS.htm
Targeted Cells:
The virus, entering through which various routes, act primarily on the following cells:
* Lymphoreticular system:
o CD4+ T-Helper cells
o Macrophages
o Monocytes
o B-lymphocytes
* Certain endothelial cells
* Central nervous system:
o Microglia of the nervous system
o Astrocytes
o Oligodendrocytes
o Neurones – indirectly by the action of cytokines and the gp-120
Source: The Wikipedia site had the above list of affected somatic cells.
Note: the gametic cells, responsible for sexual reproduction are not on the list.
* What are the treatments for AIDS?
HAART, or Highly Active Anti-retro viral Therapy is a cocktail taken multiple times per day by aids patients. This is the new front line medication for HIV/AIDS. This chemotherapy can halt the progression of the disease dramatically.
http://www.healthscout.com/ency/68/101/main.html
* Had I heard of a patient who is clear of HIV for 2 years post bone marrow transplant?
Yes, I believe that I had heard of a person in Germany who was immune and they did a graft to try and get the immune cells to multiply.
Wikipedia had this to say about the German patient:
"In Berlin, Germany, a 42-year-old leukemia patient infected with HIV for more than a decade was given an experimental transplant of bone marrow with cells that contained an unusual natural variant of the CCR5 cell-surface receptor. This CCR5-Δ32 variant has been shown to make some cells from people who are born with it resistant to infection with some strains of HIV. Almost two years after the transplant, and even after the patient reportedly stopped taking anti-retro viral medications, HIV has not been detected in the patient's blood.[126]"
Thanks again to my fellow students for your questions and especially for your corrections.
I look forward to the rest of the presentations!!!
MCB
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