Evidence map›Paper›PMID 28097769›Full record

ArticleProtein science : a publication of the Protein Society2017

High resolution crystal structures of human kynurenine aminotransferase-I bound to PLP cofactor, and in complex with aminooxyacetate.

Naveed A Nadvi, Noeris K Salam, Joohong Park, Fady N Akladios, Vimal Kapoor, Charles A Collyer, Mark D Gorrell, William Bret Church

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

Article in Protein science : a publication of the Protein Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.6field-weighted citation impact, top 39% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. HCellular and molecular life sciences : CMLS · 2022
    Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. 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 2 institutions in 1 country.

Naveed A NadviGroup in Biomolecular Structure and Informatics, Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia.
Noeris K SalamGroup in Biomolecular Structure and Informatics, Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia.
Joohong ParkMolecular Hepatology, Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Fady N AkladiosGroup in Biomolecular Structure and Informatics, Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia.
Vimal KapoorSchool of Medicine and Pharmacology, The University of Western Australia, Perth, Western, Australia, Australia.
Charles A CollyerSchool of Molecular Bioscience, University of Sydney, Sydney, New South Wales, Australia.
Mark D GorrellMolecular Hepatology, Centenary Institute and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
William Bret ChurchGroup in Biomolecular Structure and Informatics, Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0002-8033-5518
The University of Sydney · AUThe University of Western Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In this study, we report two high-resolution structures of the pyridoxal 5' phosphate (PLP)-dependent enzyme kynurenine aminotransferase-I (KAT-I). One is the native structure with the cofactor in the PLP form bound to Lys247 with the highest resolution yet available for KAT-I at 1.28 Å resolution, and the other with the general PLP-dependent aminotransferase inhibitor, aminooxyacetate (AOAA) covalently bound to the cofactor at 1.54 Å. Only small conformational differences are observed in the vicinity of the aldimine (oxime) linkage with which the PLP forms the Schiff base with Lys247 in the 1.28 Å resolution native structure, in comparison to other native PLP-bound structures. We also report the inhibition of KAT-1 by AOAA and aminooxy-phenylpropionic acid (AOPP), with IC50s of 13.1 and 5.7 μM, respectively. The crystal structure of the enzyme in complex with the inhibitor AOAA revealed that the cofactor is the PLP form with the external aldimine linkage. The location of this oxime with the PLP, which forms in place of the native internal aldimine linkage of PLP of the native KAT-I, is away from the position of the native internal aldimine, with the free Lys247 substantially retaining the orientation of the native structure. Tyr101, at the active site, was observed in two conformations in both structures.

Indexed as

Aminooxyacetic AcidCrystallography, X-RayHumansProtein DomainsPyridoxal PhosphateTransaminasesAminooxyacetic Acidkynurenine-oxoglutarate transaminasePyridoxal PhosphateTransaminasesaminotransferasekynurenic acidkynureninepyridoxyl phosphatetransferase

Identifiers

PMID28097769
PMCPMC5368072
OpenAlexW2579283575

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.