Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2020 Jun 30;10:10664. doi: 10.1038/s41598-020-65993-z

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Structural deformations of PR revealed by overlaying of PR_wt with PR_DRV^R_P30 or PR_DRV^R_P51, Panel (a) shows a superimposition of two PR_WT structures in complex with GRL-001 or GRL-003 (light and dark green tones) onto two PR_DRV^R_P30 structure in complex with GRL-001 or GRL-003 (magenta and salmon) exhibiting no major structural differences; while panel (b) shows superimposition of two PR_WT structures in complex with GRL-001 or GRL-003 (green tones) with two PR_DRV^R_P51 structures in complex with GRL-001 and GRL-003 (yellow and orange), revealing significant structural differences around E35, as indicated by an arrow. Panels (c) and (d) focus on the hydrophobic cavity, where the substitution of L33 in PR_WT [(complexed with GRL-001 in green (c)] with the F33 in PR_DRV^R_P51 [(complexed with GRL-001 in yellow (d)] causes the structural reorganization of the 30 s loop, resulting in a new hydrogen bonds pattern between E35 and R20 as shown with two grey dashed lines as shown in panel (f). Panel (e) shows the PR_WT structure in complex with GRL-001 (green), where the salt bridge between R57 and E35 connects the flap region on the top with the 30 s loops, stabilizing the flap region. However, in the PR_DRV^R_P51 structures in complex with GRL-001 (yellow), two new hydrogen bonds are newly formed between E35 and R20, as described above, resulting in a loss of the salt bridge between R57 and E35 in the PR_WT structure. Panel (g), depicting a superimposition of PR_WT and PR_DRV^R_P51, shows zoomed-in conformational changes around the flap region between PR_WT (green) and PR_DRV^R_P51 (yellow) in complex with GRL-001. Distances measured for PR_WT (green) and PR_DRV^R_P51 from amino group of P81 to amino group of G52 are indicated in green and yellow. Approximately 0.6 Å expansion of the binding pocket was measured. As shown in panel (h), depicting the structure of PR_DRV^R_P51 complexed with GRL-001, the side chain interactions of M54 with particular emphasis to the sulfur-oxygen contact as well as sulfur-proline ring interaction are identified. GRL-001 is shown in surface representation with a fluorine atom highlighted in cyan directing towards P81, forming effective fluorine-based halogen bonds with P81 ring to counters the affinity loss caused by the amino acid substitutions in PR_DRV^R_P51. (PDB IDs for GRL-001: 6MRC, GRL-003: 6MCS and GRL-142: 5TYS).