Evidence map›Paper›PMID 33439152›Full record

ArticleActa crystallographica. Section F, Structural biology communications2021

Using yeast surface display to engineer a soluble and crystallizable construct of hematopoietic progenitor kinase 1 (HPK1).

Wai L Lau, Bradley Pearce, Heather Malakian, Iyoncy Rodrigo, Dianlin Xie, Mian Gao, Frank Marsilio, Chiehying Chang, Max Ruzanov, Jodi K Muckelbauer and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta crystallographica. Section F, Structural biology communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 23% 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

4 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Frontiers in bioengineering and biotechnology · 2023
    Article
  3. Article
  4. Article
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

13 authors at 1 institution in 1 country.

Wai L LauBiologics Discovery, Bristol-Myers Squibb Research and Development, 100 Binney Street, Cambridge, MA 02142, USA.
Bradley PearceMolecular Structure and Design, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA.
Heather MalakianBiologics Discovery, Bristol-Myers Squibb Research and Development, 100 Binney Street, Cambridge, MA 02142, USA.ORCID 0000-0002-5424-0996
Iyoncy RodrigoProtein Science, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
Dianlin XieProtein Science, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
Mian GaoProtein Science, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
Frank MarsilioProtein Science, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
Chiehying ChangMolecular Structure and Design, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
Max RuzanovMolecular Structure and Design, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
Jodi K MuckelbauerMolecular Structure and Design, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.ORCID 0000-0001-7848-3178
John A NewittProtein Science, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.ORCID 0000-0001-7324-715X
Daša LipovšekBiologics Discovery, Bristol-Myers Squibb Research and Development, 100 Binney Street, Cambridge, MA 02142, USA.ORCID 0000-0001-9922-0019
Steven SheriffMolecular Structure and Design, Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA.ORCID 0000-0001-6010-6534
Bristol-Myers Squibb (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hematopoietic progenitor kinase 1 (HPK1) is an intracellular kinase that plays an important role in modulating tumor immune response and thus is an attractive target for drug discovery. Crystallization of the wild-type HPK1 kinase domain has been hampered by poor expression in recombinant systems and poor solubility. In this study, yeast surface display was applied to a library of HPK1 kinase-domain variants in order to select variants with an improved expression level and solubility. The HPK1 variant with the most improved properties contained two mutations, crystallized readily in complex with several small-molecule inhibitors and provided valuable insight to guide structure-based drug design. This work exemplifies the benefit of yeast surface display towards engineering crystallizable proteins and thus enabling structure-based drug discovery.

Indexed as

Cell Surface Display TechniquesCrystallizationCrystallography, X-RayHumansModels, MolecularMutagenesisMutationProtein DomainsProtein EngineeringProtein Kinase InhibitorsProtein Serine-Threonine KinasesRecombinant ProteinsSaccharomyces cerevisiaehematopoietic progenitor kinase 1Protein Kinase InhibitorsProtein Serine-Threonine KinasesRecombinant Proteinscrystallizabilityhematopoietic progenitor kinase 1homology modelingHPK1yeast surface display

Identifiers

PMID33439152
PMCPMC7805552
OpenAlexW3117805063

What OpenQuestion holds

Textmetadata
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.