Evidence map›Paper›PMID 27573844›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Anatomy of the β-branching enzyme of polyketide biosynthesis and its interaction with an acyl-ACP substrate.

Finn P Maloney, Lena Gerwick, William H Gerwick, David H Sherman, Janet L Smith

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
5.5field-weighted citation impact, top 4% 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

15 citing papers in PubMed, 39 citations in OpenAlex.

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  8. Development of a Pantetheine Force Field Library for Molecular Modeling.Journal of chemical information and modeling · 2021
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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

5 authors at 3 institutions in 1 country.

Finn P MaloneyLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109; Chemical Biology Doctoral Program, University of Michigan, Ann Arbor, MI 48109;
Lena GerwickCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093;
William H GerwickCenter for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093;
David H ShermanLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109; Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109;
Janet L SmithLife Sciences Institute, University of Michigan, Ann Arbor, MI 48109; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109 JanetSmith@umich.edu.
University of Michigan–Ann Arbor · USScripps Institution of Oceanography · USUniversity of California, San Diego · US

Funding

STRUCTURE AND FUNCTION OF A PURINE BIOSYNTHETIC ENZYMER01DK042303 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SMITH, JANET L. · 1990 to 2024
$6.6M
Biosynthetic Analysis of Marine Cyanobacterial PathwaysR01CA108874 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GERWICK, WILLIAM HENRY, SHERMAN, DAVID H · 2006 to 2015
$3.4M
Silicon Mechanics Compute ClusterS10OD020011 · OD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SKINIOTIS, GEORGIOS · 2015 to 2015
$490k
NCI NIH HHS R01 CA108874NIDDK NIH HHS R01 DK042303NIH HHS S10 OD020011
6 · The paper itself

Abstract

Alkyl branching at the β position of a polyketide intermediate is an important variation on canonical polyketide natural product biosynthesis. The branching enzyme, 3-hydroxy-3-methylglutaryl synthase (HMGS), catalyzes the aldol addition of an acyl donor to a β-keto-polyketide intermediate acceptor. HMGS is highly selective for two specialized acyl carrier proteins (ACPs) that deliver the donor and acceptor substrates. The HMGS from the curacin A biosynthetic pathway (CurD) was examined to establish the basis for ACP selectivity. The donor ACP (CurB) had high affinity for the enzyme (Kd = 0.5 μM) and could not be substituted by the acceptor ACP. High-resolution crystal structures of HMGS alone and in complex with its donor ACP reveal a tight interaction that depends on exquisite surface shape and charge complementarity between the proteins. Selectivity is explained by HMGS binding to an unusual surface cleft on the donor ACP, in a manner that would exclude the acceptor ACP. Within the active site, HMGS discriminates between pre- and postreaction states of the donor ACP. The free phosphopantetheine (Ppant) cofactor of ACP occupies a conserved pocket that excludes the acetyl-Ppant substrate. In comparison with HMG-CoA (CoA) synthase, the homologous enzyme from primary metabolism, HMGS has several differences at the active site entrance, including a flexible-loop insertion, which may account for the specificity of one enzyme for substrates delivered by ACP and the other by CoA.

Indexed as

Acyl Carrier ProteinAcyl Coenzyme AAmino Acid SequenceCatalytic DomainCrystallography, X-RayCyclopropanesHydroxymethylglutaryl-CoA SynthasePolyketidesPolyketide SynthasesStreptomycesSubstrate SpecificityThiazoles3-hydroxy-3-methylglutaryl-coenzyme AAcyl Carrier ProteinAcyl Coenzyme Acuracin ACyclopropanesHydroxymethylglutaryl-CoA SynthasePolyketidesPolyketide SynthasesThiazolesacyl carrier proteincuracinHMG synthasenatural productspolyketide synthase

Identifiers

PMID27573844
PMCPMC5027445
OpenAlexW2518532193

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.