Evidence map›Paper›PMID 40411433›Full record

ArticleProtein science : a publication of the Protein Society2025

Cis-nonProline peptides: Genuine occurrences and their functional roles.

Jane S Richardson, Lizbeth L Videau, Christopher J Williams, Bradley J Hintze, Steven M Lewis, David C Richardson

Abstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Review
  3. Cis-nonProline peptides: Genuine occurrences and their functional roles.Protein science : a publication of the Protein Society · 2025
    Article
  4. Article
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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

6 authors.

Jane S RichardsonDepartment of Biochemistry, Duke University, Durham, North Carolina, USA.ORCID 0000-0002-3311-2944
Lizbeth L VideauDepartment of Biochemistry, Duke University, Durham, North Carolina, USA.
Christopher J WilliamsDepartment of Biochemistry, Duke University, Durham, North Carolina, USA.ORCID 0000-0002-5808-8768
Bradley J HintzeDepartment of Biochemistry, Duke University, Durham, North Carolina, USA.ORCID 0000-0002-4871-2096
Steven M LewisDepartment of Biochemistry, Duke University, Durham, North Carolina, USA.ORCID 0000-0002-0143-1780
David C RichardsonDepartment of Biochemistry, Duke University, Durham, North Carolina, USA.ORCID 0000-0001-5069-343X

Funding

PROJECT 5 - DUKE - STRUCTURE VALIDATION AND IMPROVEMENT FOR PROTEINS AND N. ACIDSP01GM063210 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI ADAMS, PAUL DAVID · 2001 to 2021
$33.5M
MolProbity Validation & Corrections: for Crystallography, PDB & BiomedicineR01GM073919 · NIGMS · DUKE UNIVERSITY · PI RICHARDSON, DAVID CLAUDE · 2006 to 2018
$3.7M
NIGMS NIH HHS P01 GM063210NIGMS NIH HHS R01 GM073919NIH HHS NIH P01-GM063210NIH HHS NIH R01-gm073919
6 · The paper itself

Abstract

While cis peptides preceding proline can occur about 5% of the time, cis peptides preceding any other residue ("cis-nonPro" peptides) are an extremely rare feature in protein structures, of considerable importance for two opposite reasons. On one hand, their genuine occurrences are mostly found at sites critical to biological function, from the active sites of carbohydrate enzymes to rare adjacent-residue disulfide bonds. On the other hand, a cis-nonPro can easily be misfit into weak or ambiguous electron density, which led to a high incidence of unjustified cis-nonPro over the 2006-2015 decade. This paper uses high-resolution crystallographic data and especially stringent quality-filtering at the residue level to identify genuine occurrences of cis-nonPro and to survey both individual examples and broad patterns of their functionality. We explain the procedure developed to identify genuine cis-nonPro examples with almost no false positives. We then survey a large sample of the varied functional roles and structural contexts of cis-nonPro, including the uses of specific amino acids for particular purposes. We emphasize aspects not previously covered: that cis-nonPro essentially always (except for vicinal disulfides) occurs in well-ordered structure, and especially the great concentration of occurrence in proteins that process or bind carbohydrates (identified by occurrence on the CAZy website).

Indexed as

PeptidesProlineCrystallography, X-RayModels, MolecularProtein ConformationPeptidesProlineasp‐cis‐aspcis‐nonPro overrepresented in carbohydrate‐active enzymesCys‐cis‐CysGly‐cis‐Glyincorrect cis‐nonProTyr‐cis‐X at active site in chitinases

Identifiers

PMID40411433
PMCPMC12102755

What OpenQuestion holds

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Registered trials

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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.