Flaps Morph for HIV Protease
From Proteopedia
| Line 144: | Line 144: | ||
===Flaps in Other Proteins=== | ===Flaps in Other Proteins=== | ||
| - | *[[Sandbox 215]] | + | *[[Sandbox 215]]: Omega flaps in cholesterol ester transfer protein. |
*[[Fatty acid amide hydrolase]], [[Sandbox_Reserved_921]], [[Sandbox_Reserved_922]] | *[[Fatty acid amide hydrolase]], [[Sandbox_Reserved_921]], [[Sandbox_Reserved_922]] | ||
==References== | ==References== | ||
<references /> | <references /> | ||
Revision as of 00:23, 23 February 2020
Contents |
Methods
1hxw, containing the inhibitor Ritonavir, was selected in part because it is more closed than an early, unliganded wild type structure: Ile50 to Gly27 is 11.6 Å in 1hxw, vs. 16.9 Å in 3phv. (The only mutation in 1hxw is S37N.) 1tw7, with "wide open" flaps, was selected in part because its asymmetric unit contains two chains. It has many drug-resistance mutations (see table below).
The morph was generated by Proteopedia's PyMOL Morpher.
|
Wide-Open Drug-Free HIV Protease Crystal Structures[3] |
||||||
|
PDB ID |
Year |
Resolution; Rfree* |
Asymm. Unit |
Ile50 dist. |
Mutations; Comments |
Wild Type |
|
2005 |
1.3 Å; WTA* |
2 chains |
12.25 Å |
I10L, N25D, V36M, L46M, V54I, V62I, P63L, V71A, A82V, V84I, M90L | ||
|
2007 |
1.4 Å; BTA* |
1 chain |
12.2 Å |
K7Q | ||
|
2008 |
1.2 Å; A* |
1 chain |
12.19 Å |
K7Q, I33L, R41K, I63L | ||
|
Other HIV Protease Crystal Structures With Separated Flaps |
||||||
|
2014 |
1.66 Å; A* |
1 chain |
13.2 Å |
D25N; Inhibitor is between flaps | ||
|
2011 |
2.25 Å; U* |
1 chain |
11.9 Å |
V10I, N25D, E35D, V36I, L46M, A82T; Structure unreliable according to Rfree. | ||
- Rfree is categorized by FirstGlance in Jmol as A (Average), BTA (Better Than Average), U (Unreliable), WTA (Worse Than Average) at the corresponding resolution.
- I did not finish examining hits via google for 'hiv protease flaps animation'
Relevant Resources
Well-Developed, in Proteopedia
- Immunodeficiency virus protease includes morphs of flap movements and saquinavir binding. (HIV-1 protease redirects here.)
- Immunodeficiency virus protease 3D structures lists hundreds of crystal structures of HIV proteases.
- HIV Protease Inhibitor Resistance Profile
- Molecular Playground/HIV Protease Inhibitor includes an animated simulation of the protease inhibitor Ritonavir binding to the protease.
- Group:SMART:HIV-1 Subtype C Protease
- Protease
- Human Immunodeficiency Virus
- Journal:Acta_Cryst_D:S2059798319011355 Comparison of a retroviral protease crystallized as a monomer and a dimer.
Sandboxes in Proteopedia
- User:Tsung-Yi_Lin/Sandbox
- User:Dan_Huettner/Sandbox_1, User:Dan_Huettner/Sandbox_3
- User:David Canner/Sandbox HIV
- Sandbox 645
- Sandbox_Reserved_712
- Sandbox Reserved 955
- User:Nicole Maille/Sandbox 1
Flaps in Other Proteins
- Sandbox 215: Omega flaps in cholesterol ester transfer protein.
- Fatty acid amide hydrolase, Sandbox_Reserved_921, Sandbox_Reserved_922
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Martin P, Vickrey JF, Proteasa G, Jimenez YL, Wawrzak Z, Winters MA, Merigan TC, Kovari LC. "Wide-open" 1.3 A structure of a multidrug-resistant HIV-1 protease as a drug target. Structure. 2005 Dec;13(12):1887-95. PMID:16338417 doi:10.1016/j.str.2005.11.005
- ↑ Heal JW, Jimenez-Roldan JE, Wells SA, Freedman RB, Romer RA. Inhibition of HIV-1 protease: the rigidity perspective. Bioinformatics. 2012 Feb 1;28(3):350-7. doi: 10.1093/bioinformatics/btr683. PMID:22291339 doi:http://dx.doi.org/10.1093/bioinformatics/btr683
- ↑ 3.0 3.1 3.2 Yu, Y. et al., Structural insights into HIV-1 protease flap opening processes and key intermediates. 2017 RSC Advances, 7:45121-8. NOT IN PUBMED. OPEN ACCESS. DOI: 10.1039/C7RA09691G.
