Evidence map›Paper›PMID 34326456›Full record

ArticleCommunications biology2021

Cryo-EM structures of inhibitory antibodies complexed with arginase 1 provide insight into mechanism of action.

Rachel L Palte, Veronica Juan, Yacob Gomez-Llorente, Marc Andre Bailly, Kalyan Chakravarthy, Xun Chen, Daniel Cipriano, Ghassan N Fayad, Laurence Fayadat-Dilman, Symon Gathiaka and 15 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. The roles of arginases and arginine in immunity.Nature reviews. Immunology · 2025
    Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 1 institution in 3 countries.

Rachel L PalteDepartment of Discovery Chemistry, Merck & Co., Inc., Boston, MA, USA. rachel.kubiak@merck.com.ORCID http://orcid.org/0000-0001-6146-0551
Veronica JuanDepartment of Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, USA.
Yacob Gomez-LlorenteDepartment of Discovery Chemistry, Merck & Co., Inc., Kenilworth, NJ, USA.
Marc Andre BaillyDepartment of Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, USA.
Kalyan ChakravarthyDepartment of Discovery Biology, Merck & Co., Inc., Boston, MA, USA.
Xun ChenDepartment of Discovery Chemistry, Merck & Co., Inc., Kenilworth, NJ, USA.
Daniel CiprianoDepartment of Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, USA.
Ghassan N FayadDepartment of Preclinical Development, Merck & Co., Inc., Boston, MA, USA.
Laurence Fayadat-DilmanDepartment of Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, USA.
Symon GathiakaDepartment of Discovery Chemistry, Merck & Co., Inc., Boston, MA, USA.
Heiko GrebDepartment of Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, USA.
Brian HallDepartment of Discovery Biologics, Merck & Co., Inc., Boston, MA, USA.
Mas HandaDepartment of Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, USA.
Mark HsiehDepartment of Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, USA.
Esther KofmanDepartment of Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, USA.
Heping LinDepartment of Discovery Biologics, Merck & Co., Inc., Boston, MA, USA.
J Richard MillerDepartment of Discovery Biology, Merck & Co., Inc., Boston, MA, USA.
Nhung NguyenDepartment of Discovery Biologics, Merck & Co., Inc., South San Francisco, CA, USA.
Jennifer O'NeilDepartment of Discovery Oncology, Merck & Co., Inc., Boston, MA, USA.
Hussam ShaheenDepartment of Discovery Biologics, Merck & Co., Inc., Boston, MA, USA.
Eric SternerDepartment of Discovery Biologics, Merck & Co., Inc., Boston, MA, USA.
Corey StricklandDepartment of Discovery Chemistry, Merck & Co., Inc., Kenilworth, NJ, USA.
Angie SunDepartment of Discovery Biologics, Merck & Co., Inc., Boston, MA, USA.
Shane TaremiDepartment of Discovery Biologics, Merck & Co., Inc., Boston, MA, USA.
Giovanna ScapinDepartment of Discovery Chemistry, Merck & Co., Inc., Kenilworth, NJ, USA.
Merck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human Arginase 1 (hArg1) is a metalloenzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea, and modulates T-cell-mediated immune response. Arginase-targeted therapies have been pursued across several disease areas including immunology, oncology, nervous system dysfunction, and cardiovascular dysfunction and diseases. Currently, all published hArg1 inhibitors are small molecules usually less than 350 Da in size. Here we report the cryo-electron microscopy structures of potent and inhibitory anti-hArg antibodies bound to hArg1 which form distinct macromolecular complexes that are greater than 650 kDa. With local resolutions of 3.5 Å or better we unambiguously mapped epitopes and paratopes for all five antibodies and determined that the antibodies act through orthosteric and allosteric mechanisms. These hArg1:antibody complexes present an alternative mechanism to inhibit hArg1 activity and highlight the ability to utilize antibodies as probes in the discovery and development of peptide and small molecule inhibitors for enzymes in general.

Indexed as

ArginaseArginineBinding SitesCryoelectron MicroscopyOrnithineProtein BindingSubstrate SpecificityARG1 protein, humanArginaseArginineOrnithine

Identifiers

PMID34326456
PMCPMC8322407
OpenAlexW3187000210

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.