Water molecules inside protein structure affect binding of monosaccharides with HIV-1 antibody 2G12

2016 ◽  
Vol 37 (26) ◽  
pp. 2341-2348 ◽  
Author(s):  
Kaori Ueno-Noto ◽  
Keiko Takano
Keyword(s):  
Protein Structure ◽  
Water Molecules ◽  
Hiv 1 ◽  
Antibody 2G12

scholarly journals PARAMETER OPTIMIZATION AND VIRTUAL SCREENING INDONESIAN HERBAL DATABASE AS HUMAN IMMUNODEFICIENCY VIRUS -1 INTEGRASE INHIBITOR USING AUTODOCK AND VINA

2017 ◽  
Vol 9 ◽  
pp. 90
Author(s):  
Arry Yanuar ◽  
Rezi Riadhi Syahdi ◽  
Widya Dwi Aryati
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virtual Screening ◽  
Integrase Inhibitor ◽  
Water Molecules ◽  
Autodock Vina ◽  
Unit Space ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

Objective: Human immunodeficiency virus (HIV-1) is a virus that causes acquired immunodeficiency syndrome, a disease considered to be one of themost dangerous because of its high mortality, morbidity, and infectivity. The emergence of mutant HIV strains has led treatment to target proteaseas reverse transcriptase and integrase enzyme become less effective. This study aims to provide knowledge about the potential of HIV-1 integraseinhibitors for use as guiding compounds in the development of new anti-HIV drugs.Methods: This study used AutoDock and AutoDock Vina for virtual screening of the Indonesian herbal database for inhibitors of HIV-1 integrase andis validated using a database of the directory of useful decoys. Optimization was accomplished by selecting the grid size, the number of calculations,and the addition of two water molecules and a magnesium atom as cofactor.Results: This study determined that the best grid box size is 21.1725×21.1725×21.1725 in unit space size (1 unit space equals to macromolecules 1Ǻ),using AutoDock Vina with EF and AUC values, 3.93 and 0.693, respectively. Three important water molecules have meaning in molecular dockingaround the binding pocket.Conclusions: This study obtained the top ten ranked compounds using AutoDock Vina. The compounds include: Casuarinin; Myricetin-3-O-(2’’,6’’-di-O-α-rhamnosyl)-β-glucoside; 5,7,2’,4’-tetrahydroxy-6,3’-diprenylisoflavone 5-O-(4’’-rhamnosylrhamnoside); myricetin 3-robinobioside; cyanidin3-[6-(6-ferulylglucosyl)-2-xylosylgalactoside]; mesuein, cyanidin 7-(3-glucosyl-6-malonylglucoside)-4’-glucoside; kaempferol 3-[glucosyl-(1→3)-rhamnosyl-(1→6)-galactoside]; 3-O-galloylepicatechin-(4-β→8)-epicatechin-3-O-gallate; and quercetin 4’-glucuronide.

Gold Nanoparticles Coated with Oligomannosides of HIV-1 Glycoprotein gp120 Mimic the Carbohydrate Epitope of Antibody 2G12

2011 ◽  
Vol 410 (5) ◽  
pp. 798-810 ◽  
Author(s):  
Marco Marradi ◽  
Paolo Di Gianvincenzo ◽  
Pedro M. Enríquez-Navas ◽  
Olga M. Martínez-Ávila ◽  
Fabrizio Chiodo ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Carbohydrate Epitope ◽  
Glycoprotein Gp120 ◽  
Hiv 1 ◽  
Antibody 2G12

scholarly journals Structural Basis for Enhanced HIV-1 Neutralization by a Dimeric Immunoglobulin G Form of the Glycan-Recognizing Antibody 2G12

Cell Reports ◽  
2013 ◽  
Vol 5 (5) ◽  
pp. 1443-1455 ◽  
Author(s):  
Yunji Wu ◽  
Anthony P. West ◽  
Helen J. Kim ◽  
Matthew E. Thornton ◽  
Andrew B. Ward ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Structural Basis ◽  
Hiv 1 ◽  
Antibody 2G12

scholarly journals Resistance of HIV-1 to the broadly HIV-1-neutralizing, anti-carbohydrate antibody 2G12

Virology ◽  
2007 ◽  
Vol 360 (2) ◽  
pp. 294-304 ◽  
Author(s):  
Dana Huskens ◽  
Kristel Van Laethem ◽  
Kurt Vermeire ◽  
Jan Balzarini ◽  
Dominique Schols
Keyword(s):  
Hiv 1 ◽  
Antibody 2G12

ChemInform Abstract: Bis Tertiary Amide Inhibitors of the HIV-1 Protease Generated via Protein Structure-Based Iterative Design.

ChemInform ◽  
2010 ◽  
Vol 27 (43) ◽  
pp. no-no
Author(s):  
M. MELNICK ◽  
S. H. REICH ◽  
K. K. LEWIS ◽  
L. J. JUN. MITCHELL ◽  
NGUYEN DZUY NGUYEN DZUY ◽  
...  
Keyword(s):  
Protein Structure ◽  
Iterative Design ◽  
Tertiary Amide ◽  
Hiv 1

scholarly journals The utility of protein structure as a predictor of site-wise d N /d S varies widely among HIV-1 proteins

2015 ◽  
Vol 12 (111) ◽  
pp. 20150579 ◽  
Author(s):  
Austin G. Meyer ◽  
Claus O. Wilke
Keyword(s):  
Protein Structure ◽  
Reference Site ◽  
Solvent Accessibility ◽  
Relative Solvent Accessibility ◽  
Apical Surface ◽  
Structural Constraints ◽  
Functional Sites ◽  
Protease Enzyme ◽  
Evolutionary Variation ◽  
Hiv 1

Protein structure acts as a general constraint on the evolution of viral proteins. One widely recognized structural constraint explaining evolutionary variation among sites is the relative solvent accessibility (RSA) of residues in the folded protein. In influenza virus, the distance from functional sites has been found to explain an additional portion of the evolutionary variation in the external antigenic proteins. However, to what extent RSA and distance from a reference site in the protein can be used more generally to explain protein adaptation in other viruses and in the different proteins of any given virus remains an open question. To address this question, we have carried out an analysis of the distribution and structural predictors of site-wise d N /d S in HIV-1. Our results indicate that the distribution of d N /d S in HIV follows a smooth gamma distribution, with no special enrichment or depletion of sites with d N /d S at or above one. The variation in d N /d S can be partially explained by RSA and distance from a reference site in the protein, but these structural constraints do not act uniformly among the different HIV-1 proteins. Structural constraints are highly predictive in just one of the three enzymes and one of three structural proteins in HIV-1. For these two proteins, the protease enzyme and the gp120 structural protein, structure explains between 30 and 40% of the variation in d N /d S . Finally, for the gp120 protein of the receptor-binding complex, we also find that glycosylation sites explain just 2% of the variation in d N /d S and do not explain gp120 evolution independently of either RSA or distance from the apical surface.

scholarly journals Antibody 2G12 Recognizes Di-Mannose Equivalently in Domain- and Nondomain-Exchanged Forms but Only Binds the HIV-1 Glycan Shield if Domain Exchanged

2010 ◽  
Vol 84 (20) ◽  
pp. 10690-10699 ◽  
Author(s):  
Katie J. Doores ◽  
Zara Fulton ◽  
Michael Huber ◽  
Ian A. Wilson ◽  
Dennis R. Burton
Keyword(s):  
Crystallographic Analysis ◽  
Single Amino Acid ◽  
Unusual Event ◽  
Immunization Strategies ◽  
Binding Surface ◽  
Immunodeficiency Virus ◽  
High Mannose ◽  
Hiv 1 ◽  
Antibody 2G12

ABSTRACT The broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibody 2G12 targets the high-mannose cluster on the glycan shield of HIV-1. 2G12 has a unique VH domain-exchanged structure, with a multivalent binding surface that includes two primary glycan binding sites. The high-mannose cluster is an attractive target for HIV-1 vaccine design, but so far, no carbohydrate immunogen has elicited 2G12-like antibodies. Important questions remain as to how this domain exchange arose in 2G12 and how this unusual event conferred unexpected reactivity against the glycan shield of HIV-1. In order to address these questions, we generated a nondomain-exchanged variant of 2G12 to produce a conventional Y/T-shaped antibody through a single amino acid substitution (2G12 I19R) and showed that, as for the 2G12 wild type (2G12 WT), this antibody is able to recognize the same Manα1,2Man motif on recombinant gp120, Candida albicans, and synthetic glycoconjugates. However, the nondomain-exchanged variant of 2G12 is unable to bind the cluster of mannose moieties on the surface of HIV-1. Crystallographic analysis of 2G12 I19R in complex with Manα1,2Man revealed an adaptable hinge between VH and CH1 that enables the VH and VL domains to assemble in such a way that the configuration of the primary binding site and its interaction with disaccharide are remarkably similar in the nondomain-exchanged and domain-exchanged forms. Together with data that suggest that very few substitutions are required for domain exchange, the results suggest potential mechanisms for the evolution of domain-exchanged antibodies and immunization strategies for eliciting such antibodies.

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