Evidence map›Paper›PMID 28687225›Full record

ArticleBiochimica et biophysica acta. Proteins and proteomics2017

Screening cleavage of Factor XIII V34X Activation Peptides by thrombin mutants: A strategy for controlling fibrin architecture.

Madhavi A Jadhav, Whitney N Goldsberry, Sara E Zink, Kelsey N Lamb, Katelyn E Simmons, Carmela M Riposo, Boris A Anokhin, Muriel C Maurer

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta. Proteins and proteomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.8field-weighted citation impact, top 25% 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

2 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. 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

8 authors at 1 institution in 1 country.

Madhavi A JadhavChemistry Department, University of Louisville, 2320 South Brook Street, Louisville, KY 40292, USA.
Whitney N GoldsberryChemistry Department, University of Louisville, 2320 South Brook Street, Louisville, KY 40292, USA.
Sara E ZinkChemistry Department, University of Louisville, 2320 South Brook Street, Louisville, KY 40292, USA.
Kelsey N LambChemistry Department, University of Louisville, 2320 South Brook Street, Louisville, KY 40292, USA.
Katelyn E SimmonsChemistry Department, University of Louisville, 2320 South Brook Street, Louisville, KY 40292, USA.
Carmela M RiposoChemistry Department, University of Louisville, 2320 South Brook Street, Louisville, KY 40292, USA.
Boris A AnokhinChemistry Department, University of Louisville, 2320 South Brook Street, Louisville, KY 40292, USA.
Muriel C MaurerChemistry Department, University of Louisville, 2320 South Brook Street, Louisville, KY 40292, USA. Electronic address: muriel.maurer@louisville.edu.
University of Louisville · US

Funding

Factor Xlll Activation and Substrate SpecificityR01HL068440 · NHLBI · UNIVERSITY OF LOUISVILLE · PI MAURER, MURIEL C. · 2002 to 2010
$2.1M
Fibrin Clot Architecture Regulated by Factor XIIIR15HL120068 · NHLBI · UNIVERSITY OF LOUISVILLE · PI MAURER, MURIEL C. · 2013 to 2019
$1.3M
NHLBI NIH HHS R01 HL068440NHLBI NIH HHS R15 HL120068
6 · The paper itself

Abstract

In blood coagulation, thrombin converts fibrinogen into fibrin monomers that polymerize into a clot network. Thrombin also activates Factor XIII by cleaving the R37-G38 peptide bond of the Activation Peptide (AP) segment. The resultant transglutaminase introduces covalent crosslinks into the fibrin clot. A strategy to modify clot architecture would be to design FXIII AP sequences that are easier or more difficult to be thrombin-cleaved thus controlling initiation of crosslinking. To aid in this design process, FXIII V34X (28-41) Activation Peptides were kinetically ranked for cleavage by wild-type thrombin and several anticoagulant mutants. Thrombin-catalyzed hydrolysis of aromatic FXIII F34, W34, and Y34 APs was compared with V34 and L34. Cardioprotective FXIII L34 remained the variant most readily cleaved by wild-type thrombin. The potent anticoagulant thrombins W215A and W215A/E217A (missing a key substrate platform for binding fibrinogen) were best able to hydrolyze FXIII F34 and W34 APs. Thrombin I174A and L99A could effectively accommodate FXIII W34 and Y34 APs yielding kinetic parameters comparable to FXIII AP L34 with wild-type thrombin. None of the aromatic FXIII V34X APs could be hydrolyzed by thrombin Y60aA. FXIII F34 and W34 are promising candidates for FXIII - anticoagulant thrombin systems that could permit FXIII-catalyzed crosslinking in the presence of reduced fibrin formation. By contrast, FXIII Y34 with thrombin (Y60aA or W215A/E217A) could help assure that both fibrin clot formation and protein crosslinking are hindered. Regulating the activation of FXIII is predicted to be a strategy for helping to control fibrin clot architecture and its neighboring environments.

Indexed as

AnticoagulantsBlood CoagulationFactor XIIIFibrinFibrinogenHumansHydrolysisIntercellular Signaling Peptides and ProteinsKineticsPeptide FragmentsPeptidesProtein BindingSubstrate SpecificityThrombinTransglutaminasesAnticoagulantsFactor XIIIfactor XIII activation peptideFibrinFibrinogenIntercellular Signaling Peptides and ProteinsPeptide FragmentsPeptidesThrombinTransglutaminasesCoagulationFactor XIIIKineticsSerine proteaseThrombinTransglutaminase

Identifiers

PMID28687225
PMCPMC5600292
OpenAlexW2726928635

What OpenQuestion holds

Textmetadata
LicenceTDM
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.