Evidence map›Paper›PMID 39397789›Full record

ArticleActa crystallographica. Section F, Structural biology communications2024

Improving the diffraction quality of heat-shock protein 47 crystals.

Kevin Kish, Stephen Cobell, Nicolas Szapiel, Chunhong Yan, John A Newitt, Jeffrey Tredup, Iyoncy Rodrigo, Elizabeth Tomasco, Mian Gao, Frank Marsilio and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta crystallographica. Section F, Structural biology communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

17 authors.

Kevin KishMolecular Structure & Design, Bristol Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.ORCID 0009-0002-1104-698X
Stephen CobellMolecular Structure & Design, Bristol Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
Nicolas SzapielProtein Science, Bristol Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
Chunhong YanProtein Science, Bristol Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.ORCID 0000-0003-2005-4842
John A NewittProtein Science, Bristol Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.ORCID 0000-0001-7324-715X
Jeffrey TredupProtein Science, Bristol Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
Iyoncy RodrigoProtein Science, Bristol Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
Elizabeth TomascoProtein Science, Bristol Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.ORCID 0009-0005-5224-4909
Mian GaoBiologics & Platforms, Bristol Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
Frank MarsilioBiologics & Platforms, Bristol Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.
John HaugnerDiscovery Biotherapeutics, Bristol Myers Squibb Research & Development, Cambridge, MA 02141, USA.ORCID 0009-0008-1011-7225
Dasa LipovšekDiscovery Biotherapeutics, Bristol Myers Squibb Research & Development, Cambridge, MA 02141, USA.ORCID 0000-0001-9922-0019
Bi DengDiscovery Biotherapeutics, Bristol Myers Squibb Research & Development, Cambridge, MA 02141, USA.ORCID 0009-0006-8996-2231
Patrick BousquetDiscovery Biotherapeutics, Bristol Myers Squibb Research & Development, Cambridge, MA 02141, USA.
Yihong ZhangDiscovery Biotherapeutics, Bristol Myers Squibb Research & Development, Cambridge, MA 02141, USA.ORCID 0009-0000-7453-8450
Holly SchmidtDiscovery Biotherapeutics, Bristol Myers Squibb Research & Development, Cambridge, MA 02141, USA.
Steven SheriffMolecular Structure & Design, Bristol Myers Squibb Research & Development, PO Box 4000, Princeton, NJ 08543-4000, USA.ORCID 0000-0001-6010-6534

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Heat-shock protein 47 (HSP47) is a potential target for inhibitors that ameliorate fibrosis by reducing collagen assembly. In an effort to develop a structure-based drug-design system, it was not possible to replicate a previous literature result (PDB entry 4au4) for apo dog HSP47; instead, crystal forms were obtained in which pairs of dog HSP47 molecules interacted through a noncleavable C-terminal His-tag to build up tetramers, all of which had multiple molecules of HSP47 in the asymmetric unit and none of which diffracted as well as the literature precedent. To overcome these difficulties, a two-pronged approach was followed: (i) the His-tag was moved from the C-terminus to the N-terminus and was made cleavable, and (ii) Adnectin (derived from the tenth domain of human fibronectin type III) crystallization chaperones were developed. Both approaches provided well diffracting crystals, but the latter approach yielded crystal forms with only one or two HSP47 complexes per asymmetric unit, which made model building less onerous.

Indexed as

CrystallizationHSP47 Heat-Shock ProteinsAnimalsCrystallography, X-RayDogsEscherichia coliFibronectinsGene ExpressionHumansModels, MolecularRecombinant ProteinsFibronectinsHSP47 Heat-Shock ProteinsRecombinant ProteinsC- and N-terminal His-tagscrystallization chaperonesHSP47

Identifiers

PMID39397789
PMCPMC11533366

What Socratic 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 Socratic graph.