Evidence map›Paper›PMID 31467312›Full record

ArticleScientific reports2019

Biosynthesis of Hyaluronic acid polymer: Dissecting the role of sub structural elements of hyaluronan synthase.

Garima Agarwal, Krishnan K V, Shashi Bala Prasad, Anirban Bhaduri, Guhan Jayaraman

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

20 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Hyaluronic Acid and Its Synthases-Current Knowledge.International journal of molecular sciences · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Prospective bacterial and fungal sources of hyaluronic acid: A review.Computational and structural biotechnology journal · 2022
    Review
  15. Article
  16. Collagen- and hyaluronic acid-based hydrogels and their biomedical applications.Materials science & engineering. R, Reports : a review journal · 2021
    Article
  17. Article
  18. Article
  19. Review
  20. 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

5 authors at 2 institutions in 1 country.

Garima AgarwalMaterials Simulation group, Samsung Advanced Institute of Technology, Samsung R&D Institute, Bengaluru, Karnataka, 560037, India. g.agarwal@samsung.com.
Krishnan K VDepartment of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, India.
Shashi Bala PrasadDepartment of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, India.
Anirban BhaduriMaterials Simulation group, Samsung Advanced Institute of Technology, Samsung R&D Institute, Bengaluru, Karnataka, 560037, India.
Guhan JayaramanDepartment of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600036, India. guhanj@iitm.ac.in.ORCID http://orcid.org/0000-0003-0084-162X
Indian Institute of Technology Madras · INSamsung (India) · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hyaluronic acid (HA) based biomaterials have several biomedical applications. HA biosynthesis is catalysed by hyaluronan synthase (HAS). The unavailability of 3-D structure of HAS and gaps in molecular understanding of HA biosynthesis process pose challenges in rational engineering of HAS to control HA molecular weight and titer. Using in-silico approaches integrated with mutation studies, we define a dictionary of sub-structural elements (SSE) of the Class I Streptococcal HAS (SeHAS) to guide rational engineering. Our study identifies 9 SSE in HAS and elucidates their role in substrate and polymer binding and polymer biosynthesis. Molecular modelling and docking assessment indicate a single binding site for two UDP-substrates implying conformationally-driven alternating substrate specificities for this class of enzymes. This is the first report hypothesizing the involvement of sites from SSE5 in polymer binding. Mutation at these sites influence HA production, indicating a tight coupling of polymer binding and synthase functions. Mutation studies show dispensable role of Lys-139 in substrate binding and a key role of Gln-248 and Thr-283 in HA biosynthesis. Based on the functional architecture in SeHAS, we propose a plausible three-step polymer extension model from its reducing end. Together, these results open new avenues for rational engineering of Class I HAS to study and regulate its functional properties and enhanced understanding of glycosyltransferases and processive enzymes.

Indexed as

Amino Acid MotifsBacterial ProteinsBiopolymersHyaluronan SynthasesHyaluronic AcidMolecular Docking SimulationMolecular WeightMutationStreptococcus equiBacterial ProteinsBiopolymersHyaluronan SynthasesHyaluronic Acid

Identifiers

PMID31467312
PMCPMC6715743
OpenAlexW2970676627

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.