4U7V: Structure Of Wild-type Hiv Protease In Complex With Degraded Photosensitive Inhibitor

Citation:
Abstract
HIV protease (PR) is required for proteolytic maturation in the late phase of HIV replication and represents a prime therapeutic target. The regulation and kinetics of viral polyprotein processing and maturation are currently not understood in detail. Here we design, synthesize, validate and apply a potent, photodegradable HIV PR inhibitor to achieve synchronized induction of proteolysis. The compound exhibits subnanomolar inhibition in vitro. Its photolabile moiety is released on light irradiation, reducing the inhibitory potential by 4 orders of magnitude. We determine the structure of the PR-inhibitor complex, analyze its photolytic products, and show that the enzymatic activity of inhibited PR can be fully restored on inhibitor photolysis. We also demonstrate that proteolysis of immature HIV particles produced in the presence of the inhibitor can be rapidly triggered by light enabling thus to analyze the timing, regulation and spatial requirements of viral processing in real time.
PDB ID: 4U7VDownload
MMDB ID: 128093
PDB Deposition Date: 2014/7/31
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 1.38  Å
Source Organism:
Similar Structures:
Biological Unit for 4U7V: dimeric; determined by author and by software (PISA)
Molecular Components in 4U7V
Label Count Molecule
Proteins (2 molecules)
2
V-1 Protease
Molecule annotation
Chemicals (3 molecules)
1
2
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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