Immunodeficiency virus protease

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 3: Line 3:
===Structure of HIV-1 Protease===
===Structure of HIV-1 Protease===
-
The X-ray structure of HIV-1 protease reveals that it is composed of <scene name='User:David_Canner/Sandbox_HIV/Identical_subunits/1'>two symmetrically related subunits</scene>, each consisting of 99 amino acid residues. The subunits come together in such as way as to <scene name='User:David_Canner/Sandbox_HIV/Tunnel/1'>form a tunnel where they meet</scene>. This tunnel is of critical importance because the active site of the protease is located in its interior. The active site consists of <scene name='User:David_Canner/Sandbox_HIV/Catalytic_triad/3'> two Asp-Thr-Gly conserved sequences</scene>, making it a member of the aspartyl protease family. The two Asp's are <scene name='User:David_Canner/Sandbox_HIV/Catalytic_asp/1'>essential catalytic residues</scene> that activate a water molecule to hydrolytically cleave the polyprotein that binds in the tunnel.<ref>PMID:1799632</ref> You may be wondering how a polyprotein makes its way into the active-site tunnel, as the<scene name='User:David_Canner/Sandbox_HIV/Narrow_tunnel/1'> tunnel appears to be too narrow </scene> to admit it. The key is the two flexible flaps on the top of the tunnel that <scene name='User:David_Canner/Sandbox_HIV/Hiv_tunnel_morph/3'>move to allow proteins </scene>to enter the tunnel. The flaps <scene name='User:David_Canner/Sandbox_HIV/Hiv_tunnel_morph_flaps/2'>undergo a dramatic movement</scene>, shifting from an open to a closed conformation to bind the target in an appropriate conformation for cleavage.
+
The X-ray structure of HIV-1 protease reveals that it is composed of <scene name='User:David_Canner/Sandbox_HIV/Identical_subunits/1'>two symmetrically related subunits</scene>, each consisting of 99 amino acid residues. The subunits come together in such as way as to <scene name='User:David_Canner/Sandbox_HIV/Tunnel/1'>form a tunnel where they meet</scene>. This tunnel is of critical importance because the active site of the protease is located in its interior. The active site consists of <scene name='User:David_Canner/Sandbox_HIV/Catalytic_triad/3'> two Asp-Thr-Gly conserved sequences</scene>, making it a member of the aspartyl protease family. The two Asp's are <scene name='User:David_Canner/Sandbox_HIV/Catalytic_asp/1'>essential catalytic residues</scene> that protonate the carbonyl to make the carbon more electrophilic for the incoming <scene name='31/315240/Saquinavir_cat_water/2'>water</scene>. You may be wondering how a polyprotein makes its way into the active-site tunnel, as the<scene name='User:David_Canner/Sandbox_HIV/Narrow_tunnel/1'> tunnel appears to be too narrow </scene> to admit it. The key is the two flexible flaps on the top of the tunnel that <scene name='User:David_Canner/Sandbox_HIV/Hiv_tunnel_morph/3'>move to allow proteins </scene>to enter the tunnel. The flaps <scene name='User:David_Canner/Sandbox_HIV/Hiv_tunnel_morph_flaps/2'>undergo a dramatic movement</scene>, shifting from an open to a closed conformation to bind the target in an appropriate conformation for cleavage.
===Medical Implications===
===Medical Implications===

Revision as of 18:33, 21 February 2014

Structure of HIV Protease (PDB code 2nmz)

Drag the structure with the mouse to rotate

3D Structures of HIV-1 protease

  1. Virus protease

Additional Resources

For additional information, see: Human Immunodeficiency Virus

References

  1. 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
  2. Naicker P, Achilonu I, Fanucchi S, Fernandes M, Ibrahim MA, Dirr HW, Soliman ME, Sayed Y. Structural insights into the South African HIV-1 subtype C protease: impact of hinge region dynamics and flap flexibility in drug resistance. J Biomol Struct Dyn. 2012 Nov 12. PMID:23140382 doi:10.1080/07391102.2012.736774
Personal tools