Evidence map›Paper›PMID 23944979›Full record

ArticleBiochemistry2013

Thermodynamic signatures of the antigen binding site of mAb 447-52D targeting the third variable region of HIV-1 gp120.

April Killikelly, Hui-Tang Zhang, Brett Spurrier, Constance Williams, Miroslaw K Gorny, Susan Zolla-Pazner, Xiang-Peng Kong

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 21 citations in OpenAlex.

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  6. Computational-guided determination of the functional role of 447-52D long CDRH3.Protein engineering, design & selection : PEDS · 2018
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

April KillikellyDepartments of Biochemistry and Molecular Pharmacology and ‡Department of Pathology, New York University School of Medicine , New York, New York 10016, United States.
Hui-Tang Zhang
Brett Spurrier
Constance Williams
Miroslaw K Gorny
Susan Zolla-Pazner
Xiang-Peng Kong
VA NY Harbor Healthcare System · US

Funding

Vaccines to Induce Functional Antibodies Targeting the V2 Loop P01AI100151 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WANG, SHIXIA · 2012 to 2017
$15.4M
PROTECTIVE HUMAN MONOCLONAL ANTIBODIES TO HIV1R01HL059725 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ZOLLA-PAZNER, SUSAN B · 1997 to 2014
$8.8M
Training program in Molecular BiophysicsT32GM088118 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI STOKES, DAVID L. · 2010 to 2019
$1.8M
NHLBI NIH HHS HL059725NHLBI NIH HHS R01 HL059725NIAID NIH HHS AI100151NIAID NIH HHS P01 AI100151NIGMS NIH HHS T32 GM088118
6 · The paper itself

Abstract

The third variable region (V3) of HIV-1 gp120 plays a key role in viral entry into host cells; thus, it is a potential target for vaccine design. Human monoclonal antibody (mAb) 447-52D is one of the most broadly and potently neutralizing anti-V3 mAbs. We further characterized the 447-52D epitope by determining a high-resolution crystal structure of the Fab fragment in complex with a cyclic V3 and interrogated the antigen-antibody interaction by a combination of site-specific mutagenesis, isothermal titration calorimetry (ITC) and neutralization assays. We found that 447-52D's neutralization capability is correlated with its binding affinity and at 25 °C the Gibbs free binding energy is composed of a large enthalpic component and a small favorable entropic component. The large enthalpic contribution is due to (i) an extensive hydrogen bond network, (ii) a π-cation sandwiching the V3 crown apex residue Arg(315), and (iii) a salt bridge between the 447-52D heavy chain residue Asp(H95) and Arg(315). Arg(315) is often harbored by clade B viruses; thus, our data explained why 447-52D preferentially neutralizes clade B viruses. Interrogation of the thermodynamic signatures of residues at the antigen binding interface gives key insights into their contributions in the antigen-antibody interaction.

Indexed as

Amino Acid SequenceAntibodies, MonoclonalAntigen-Antibody ReactionsBinding Sites, AntibodyCrystallography, X-RayEpitopesHIV-1HIV AntibodiesHIV Envelope Protein gp120HumansHydrogen BondingImmunoglobulin Fab FragmentsModels, MolecularMutagenesis, Site-DirectedNeutralization TestsThermodynamicsAntibodies, MonoclonalEpitopesHIV AntibodiesHIV Envelope Protein gp120Immunoglobulin Fab Fragments

Identifiers

PMID23944979
PMCPMC4119751
OpenAlexW2088662286

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.