Search: L773:1097 0134 OR L773:0887 3585 >
On the orientation ...
On the orientation of the catalytic dyad in aspartic proteases
-
- Friedman, Ran (author)
- University of Zürich, Switzerland,Computational Chemistry and Biochemistry (CCBG)
-
Caflisch, A (author)
-
(creator_code:org_t)
- Wiley, 2010
- 2010
- English.
-
In: Proteins. - : Wiley. - 0887-3585 .- 1097-0134. ; 78:6, s. 1575-1582
- Related links:
-
https://urn.kb.se/re...
-
show more...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- The recent re-refinement of the X-ray structure of apo plasmepsin II from Plasmodium falciparum suggests that the two carboxylate groups in the catalytic dyad are noncoplanar, (Robbins et al., Acta Crystallogr D Biol Crystallogr 2009;65: 294–296) in remarkable contrast with the vast majority of structures of aspartic proteases. Here, evidence for the noncoplanarity of the catalytic aspartates is provided by analysis of multiple explicit water molecular dynamics (MD) simulations of plasmepsin II, human β-secretase, and HIV-protease. In the MD runs of plasmepsin II, the angle between the planes of the two carboxylates of the catalytic dyad is almost always in the range 60°–120°, in agreement with the perpendicular orientation in the re-refined X-ray structure. The noncoplanar arrangement is prevalent also in the β-secretase simulations, as well as in the runs with the inhibitor-bound proteases. Quantum-mechanics calculations provide further evidence that before catalysis the noncoplanar arrangement is favored energetically in eukaryotic aspartic proteases. Remarkably, the coplanar orientation of the catalytic dyad is observed in MD simulations of HIV-protease at 100 K but not at 300 K, which indicates that the noncoplanar arrangement is favored by conformational entropy. This finding suggests that the coplanar orientation in the crystal structures of apo aspartic proteases is promoted by the very low temperature used for data collection (usually around 100 K).
Subject headings
- NATURVETENSKAP -- Kemi -- Teoretisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Theoretical Chemistry (hsv//eng)
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
Keyword
- plasmepsin; beta-secretase; molecular dynamics; density functional theory; hiv protease; scc-dftb; m06
- Natural Science
- Naturvetenskap
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
-
Proteins
(Search for host publication in LIBRIS)
To the university's database