Sandbox GGC4
From Proteopedia
| (12 intermediate revisions not shown.) | |||
| Line 5: | Line 5: | ||
<StructureSection load='3VEV' size='340' side='right' caption='Caption for this structure' scene=''> | <StructureSection load='3VEV' size='340' side='right' caption='Caption for this structure' scene=''> | ||
| - | + | ||
| - | + | ||
== Function == | == Function == | ||
| Line 18: | Line 17: | ||
== Relevance == | == Relevance == | ||
| - | Once again, if the structure of the protease enzyme changes due to mutations, the protease inhibitors will not be effective in preventing viral maturation. The relevance of these mutations can be seen in the active site expansion that takes place, especially at residue positions 82 and 84, among others. Here, it can be seen that the V82A and the I84V mutation causes the distance | + | Once again, if the structure of the protease enzyme changes due to mutations, the protease inhibitors will not be effective in preventing viral maturation. The relevance of these mutations can be seen in the active site expansion that takes place, especially at <scene name='75/752268/Mutations_v82a_and_i84v/1'>residue positions 82 and 84</scene>, among others. Here, it can be seen that the V82A and the I84V mutation causes the distance between the active site flap to become wider as the amino acid side chains become shorter. The change in the distance of amino acid 83,84,182 and 184 is approximately 1.5 A each in amino acid residues according to Logsdon et al, 2004.This conformational change reduces the binding affinity of the protease inhibitor to the active site. |
== Structural highlights == | == Structural highlights == | ||
| + | Other notable structural highlights include the 1. <scene name='75/752268/Inhibitor_binding_site_of_mut1/1'>Inhibitor Binding Site of Mutated HIV-1 Protease</scene>, | ||
| + | 2. <scene name='75/752268/Active_site_flap/1'>Active Site Flap of Mutated HIV-1 Protease</scene>, | ||
| + | 3. <scene name='75/752268/Alpha-d-glucose/1'>Interaction with Alpha-D-glucose</scene>, and | ||
| + | 4. <scene name='75/752268/Catalytic_residue_shift/1'>Catalytic Residue Shift | ||
| + | </scene> | ||
| - | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
| + | Logsdon BC, Vickrey JF, Martin P, Proteasa G, Koepke JI, Terlecky SR, Wawrzak Z, Winters MA, Merigan TC, Kovari LC. Crystal structures of a multidrug-resistant human immunodeficiency virus type 1 protease reveal an expanded active-site cavity. J Virol. 2004 Mar;78(6):3123-32. doi: 10.1128/jvi.78.6.3123-3132.2004. PMID: 14990731; PMCID: PMC354404. | ||
<references/> | <references/> | ||
| + | Munshi S, Chen Z, Li Y, Olsen DB, Fraley ME, Hungate RW, Kuo LC. Rapid X-ray diffraction analysis of HIV-1 protease-inhibitor complexes: inhibitor exchange in single crystals of the bound enzyme. Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):1053-60. doi: 10.1107/s0907444998003588. PMID: 9757136. | ||
Current revision
HIV-1 Protease
An infection of the Human Immuno-deficiency Virus can cause Acquired Immunodeficiency Syndrome (AIDS). HIV attacks the CD4 T cells that are an essential part of the cell-mediated immune response, without which the immune system cannot fight against other infections or cancers, causing AIDS. There are currently 37 million people worldwide living with HIV/AIDS, with approximately 1 million new cases each year along with approximately 1 million deaths a year.
Antiretroviral Therapy is one of the HIV treatments that is most effective as the combinations of different medicines reduce the viral load to become undetectable and non-transmissible and also allows the immune system to recuperate and increase the CD4 count. Protease Inhibitors are one of the FDA approved medicines that target the viral Aspartyl Protease to prevent the HIV from making more copies of itself.
| |||||||||||
References
Logsdon BC, Vickrey JF, Martin P, Proteasa G, Koepke JI, Terlecky SR, Wawrzak Z, Winters MA, Merigan TC, Kovari LC. Crystal structures of a multidrug-resistant human immunodeficiency virus type 1 protease reveal an expanded active-site cavity. J Virol. 2004 Mar;78(6):3123-32. doi: 10.1128/jvi.78.6.3123-3132.2004. PMID: 14990731; PMCID: PMC354404.
Munshi S, Chen Z, Li Y, Olsen DB, Fraley ME, Hungate RW, Kuo LC. Rapid X-ray diffraction analysis of HIV-1 protease-inhibitor complexes: inhibitor exchange in single crystals of the bound enzyme. Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):1053-60. doi: 10.1107/s0907444998003588. PMID: 9757136.
