User:David Canner/Sandbox HIV: Difference between revisions

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Human Immunodeficiency Virus is a notoriously lethal virus that is known to cause AIDS. It is a homodimeric protein made by the HIV virus that is crucial to the virus's infectious capacity. The virus makes certain proteins that need to be cleaved, in order to transform into mature, fully-functional proteins that can allow the virus to infect new cells. HIV-1 protease is responsible for cleaving these nascent proteins into their mature form.

Structure of HIV-1 Protease

Looking at the structure of HIV-1 protease, we see that the protein is composed of , each consisting of identical 99 amino acid chains. The subunits come together in such as way as to . This tunnel is of critical importance as it is the location where nascent proteins are bound before cleavage. In the middle of the tunnel is the active site of the protease:. The two Asp's act as in the active site and use a water molecule to help break the protein chain that binds in the tunnel. ^[1] You may be wondering how a protein to be cleaved makes its way into the active-site tunnel, as the. The key is the two flexible flaps on the top of the tunnel that can to enter the tunnel. The flaps , shifting from an open to closed conformation to securly binding its target in an appropriate conformation for cleavage.

Medical Implications

There currently is no cure or vaccine against contracting HIV. AIDS researchers, however, have discovered treatments that can slow progression of the HIV virus, thanks in large part to our understanding of the structure of HIV-1 protease. was the the first protease inhibitor approved by the FDA for the treatment of HIV. It inhibits HIV-1 protease by , preventing nascent peptides from entering and .^[2] Saquinavir effectively acts like an uncleavable ligand, highlighted by the protease flaps undergoing upon binding. Other drugs used to treat patients infected with the HIV virus which inhibit include (1hsg), (1hxw), and (1ohr).

Additional ResourcesAdditional Resources

For additional information, see: Human Immunodeficiency Virus

ReferencesReferences

↑ Spinelli S, Liu QZ, Alzari PM, Hirel PH, Poljak RJ. The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU. Biochimie. 1991 Nov;73(11):1391-6. PMID:1799632
↑ Tie Y, Kovalevsky AY, Boross P, Wang YF, Ghosh AK, Tozser J, Harrison RW, Weber IT. Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir. Proteins. 2007 Apr 1;67(1):232-42. PMID:17243183 doi:10.1002/prot.21304

[1] Spinelli S, Liu QZ, Alzari PM, Hirel PH, Poljak RJ. The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU. Biochimie. 1991 Nov;73(11):1391-6. PMID:1799632

[2] Tie Y, Kovalevsky AY, Boross P, Wang YF, Ghosh AK, Tozser J, Harrison RW, Weber IT. Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavir. Proteins. 2007 Apr 1;67(1):232-42. PMID:17243183 doi:10.1002/prot.21304

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 <StructureSection load='2nmz' size='500' side='right' background='none' scene='User:David_Canner/Sandbox_HIV/Opening/2' caption='Structure of HIV Protease'>
 [[Image:CannergreyHIV2.png|220px|left]][[Human Immunodeficiency Virus]] is a notoriously lethal virus that is known to cause AIDS. It is a homodimeric protein made by the HIV virus that is crucial to the virus's infectious capacity.  The virus makes certain proteins that need to be cleaved, in order to transform into mature, fully-functional proteins that can allow the virus to infect new cells.  HIV-1 protease is responsible for cleaving these nascent proteins into their mature form.