Crystal structures of the methyltransferase and helicase from the ZIKA 1947 MR766 Uganda strain

2017 ◽  
Vol 73 (9) ◽  
pp. 767-774 ◽  
Author(s):  
Malgorzata Bukrejewska ◽  
Urszula Derewenda ◽  
Malwina Radwanska ◽  
Daniel A. Engel ◽  
Zygmunt S. Derewenda
Keyword(s):  
Crystal Structures ◽  
Zika Virus ◽  
Bound States ◽  
Nonstructural Proteins ◽  
Induced Fit ◽  
Conformational Selection

Two nonstructural proteins encoded byZika virusstrain MR766 RNA, a methyltransferase and a helicase, were crystallized and their structures were solved and refined at 2.10 and 2.01 Å resolution, respectively. The NS5 methyltransferase contains a boundS-adenosyl-L-methionine (SAM) co-substrate. The NS3 helicase is in the apo form. Comparison with published crystal structures of the helicase in the apo, nucleotide-bound and single-stranded RNA (ssRNA)-bound states suggests that binding of ssRNA to the helicase may occur through conformational selection rather than induced fit.

Association/dissociation Mechanisms of Intrinsically Disordered Region of Protein Beyond Conformational Selection and Induced Fit

2019 ◽  
Author(s):  
Duy Phuoc Tran ◽  
Akio Kitao
Keyword(s):  
Free Energy ◽  
Transcriptional Activation ◽  
Binding Free Energy ◽  
Energy Structure ◽  
Induced Fit ◽  
Hydrogen Bond Formation ◽  
Conformational Selection ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Region ◽  
Dissociation Mechanisms

<p>We investigate association and dissociation mechanisms of a typical intrinsically disordered region (IDR), transcriptional activation subdomain of tumor repressor protein p53 (TAD-p53) with murine double-minute clone 2 protein (MDM2). Using the combination of cycles of association and dissociation parallel cascade molecular dynamics, multiple standard MD, and Markov state model, we are successful in obtaining the lowest free energy structure of MDM2/TAD-p53 complex as the structure very close to that in crystal without prior knowledge. This method also reproduces the experimentally measured standard binding free energy, and association and dissociation rate constants solely with the accumulated MD simulation cost of 11.675 μs, in spite of the fact that actual dissociation occurs in the order of a second. Although there exist a few complex intermediates with similar free energies, TAD-p53 first binds MDM2 as the second lowest free energy intermediate dominantly (> 90% in flux), taking a form similar to one of the intermediate structures in its monomeric state. The mechanism of this step has a feature of conformational selection. In the second step, dehydration of the interface, formation of π-π stackings of the side-chains, and main-chain relaxation/hydrogen bond formation to complete α-helix take place, showing features of induced fit. In addition, dehydration (dewetting) is a key process for the final relaxation around the complex interface. These results demonstrate a more fine-grained view of the IDR association/dissociation beyond classical views of protein conformational change upon binding.</p>

From Selection to Instruction and Back — Competing Conformational Selection and Induced Fit Pathways in Abiotic Hosts

2021 ◽  
Author(s):  
Jovica D Badjic ◽  
Radoslav Z Pavlović ◽  
Remy F Lalisse ◽  
Alexandar L Hansen ◽  
Christopher A Waudby ◽  
...  
Keyword(s):  
Induced Fit ◽  
Conformational Selection

scholarly journals New crystal structures of adenylate kinase fromStreptococcus pneumoniaeD39 in two conformations

2014 ◽  
Vol 70 (11) ◽  
pp. 1468-1471
Author(s):  
Trung Thanh Thach ◽  
Sangho Lee
Keyword(s):  
Crystal Structures ◽  
Adenylate Kinase ◽  
Bound States ◽  
Critical Role ◽  
Unit Cell ◽  
Unit Cell Parameters ◽  
Space Group ◽  
Cell Parameters ◽  
Ligand Free ◽  
Adenylate Kinases

Adenylate kinases (AdKs; EC 2.7.3.4) play a critical role in intercellular homeostasis by the interconversion of ATP and AMP to two ADP molecules. Crystal structures of adenylate kinase fromStreptococcus pneumoniaeD39 (SpAdK) have recently been determined using ligand-free and inhibitor-bound crystals belonging to space groupsP21andP1, respectively. Here, new crystal structures of SpAdK in ligand-free and inhibitor-bound states determined at 1.96 and 1.65 Å resolution, respectively, are reported. The new ligand-free crystal belonged to space groupC2, with unit-cell parametersa= 73.5,b= 54.3,c= 62.7 Å, β = 118.8°. The new ligand-free structure revealed an open conformation that differed from the previously determined conformation, with an r.m.s.d on Cαatoms of 1.4 Å. The new crystal of the complex with the two-substrate-mimicking inhibitorP1,P5-bis(adenosine-5′-)pentaphosphate (Ap5A) belonged to space groupP1, with unit-cell parametersa= 53.9,b= 62.3,c= 63.0 Å, α = 101.9, β = 112.6, γ = 89.9°. Despite belonging to the same space group as the previously reported crystal, the new Ap5A-bound crystal contains four molecules in the asymmetric unit, compared with two in the previous crystal, and shows slightly different lattice contacts. These results demonstrate that SpAdK can crystallize promiscuously in different forms and that the open structure is flexible in conformation.

Conformational Selection versus Induced Fit in Kinases: The Case of PI3K-γ

2011 ◽  
Vol 51 (3) ◽  
pp. 642-646 ◽  
Author(s):  
Marco D'Abramo ◽  
Obdulia Rabal ◽  
Julen Oyarzabal ◽  
Francesco Luigi Gervasio
Keyword(s):  
Induced Fit ◽  
Conformational Selection

scholarly journals Crystal Structures of S100A6 in the Ca2+-Free and Ca2+-Bound States

Structure ◽  
2002 ◽  
Vol 10 (4) ◽  
pp. 557-567 ◽  
Author(s):  
Ludovic R. Otterbein ◽  
Jolanta Kordowska ◽  
Carlos Witte-Hoffmann ◽  
C.-L.Albert Wang ◽  
Roberto Dominguez
Keyword(s):  
Crystal Structures ◽  
Bound States

scholarly journals A Role for Both Conformational Selection and Induced Fit in Ligand Binding by the LAO Protein

2011 ◽  
Vol 7 (5) ◽  
pp. e1002054 ◽  
Author(s):  
Daniel-Adriano Silva ◽  
Gregory R. Bowman ◽  
Alejandro Sosa-Peinado ◽  
Xuhui Huang
Keyword(s):  
Ligand Binding ◽  
Induced Fit ◽  
Conformational Selection

A Computational Study of Competing Conformational Selection and Induced Fit in an Abiotic System

2021 ◽  
Author(s):  
Jovica D. Badjic ◽  
Christopher M Hadad ◽  
Remy F Lalisse ◽  
Radoslav Z Pavlović
Keyword(s):  
Computational Study ◽  
Elastic Band ◽  
Induced Fit ◽  
Conformational Selection

Host-guest complexations can be described by two competing mechanisms, conformational selection (CS) and induced fit (IF). In this work, we used a combination of nudged elastic band (NEB), adaptive steered...

scholarly journals Clinical, Virologic, and Immunologic Characteristics of Zika Virus Infection in a Cohort of US Patients: Prolonged RNA Detection in Whole Blood

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Hana M El Sahly ◽  
Rodion Gorchakov ◽  
Lilin Lai ◽  
Muktha S Natrajan ◽  
Shital M Patel ◽  
...  
Keyword(s):  
T Cells ◽  
Zika Virus ◽  
Whole Blood ◽  
Neutralizing Antibodies ◽  
Intracellular Cytokine Staining ◽  
Dengue Infection ◽  
Nonstructural Proteins ◽  
Zikv Infection ◽  
Rna Detection ◽  
Blood Specimens

Abstract Background Clinical, virologic, and immunologic characteristics of Zika virus (ZIKV) infections in US patients are poorly defined. Methods US subjects with suspected ZIKV infection were enrolled. Clinical data and specimens were prospectively collected for ZIKV RNA detection and serologic and cellular assays. Confirmed ZIKV infection (cases) and ZIKV-negative (controls) subjects were compared. Dengue-experienced and dengue-naïve cases were also compared. Results We enrolled 45 cases and 14 controls. Commonly reported symptoms among cases and controls were maculopapular rash (97.8% and 81.8%), fatigue (86.7% and 81.8%), and arthralgia (82.2% and 54.5%), respectively. The sensitivity (94%) and duration of infection detection (80% positivity at 65–79 days after disease onset) by polymerase chain reaction were highest in whole-blood specimens. ZIKV-neutralizing antibodies had a half-life of 105 days and were significantly higher in dengue virus–experienced cases than naïve ones (P = .046). In intracellular cytokine staining assays, the ZIKV proteins targeted most often by peripheral blood mononuclear cells from cases were structural proteins C and E for CD4+ T cells and nonstructural proteins NS3, NS5, and NS4B for CD8+ T cells. Conclusions ZIKV RNA detection was more frequent and prolonged in whole-blood specimens. Immunoglobulin G (IgG) and neutralizing antibodies, but not IgM, were influenced by prior dengue infection. Robust cellular responses to E and nonstructural proteins have potential vaccine development implications.

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