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Structure and Characterization of Phosphoglucomutase 5 from Atlantic and Baltic Herring-An Inactive Enzyme with Intact Substrate Binding

Gustafsson, Robert and Eckhard, Ulrich and Ye, Weihua and Enbody, Erik D. and Pettersson, Mats and Jemth, Per and Andersson, Leif and Selmer, Maria (2020). Structure and Characterization of Phosphoglucomutase 5 from Atlantic and Baltic Herring-An Inactive Enzyme with Intact Substrate Binding. Biomolecules. 10 , 1631
[Research article]

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Abstract

Phosphoglucomutase 5 (PGM5) in humans is known as a structural muscle protein without enzymatic activity, but detailed understanding of its function is lacking. PGM5 belongs to the alpha-D-phosphohexomutase family and is closely related to the enzymatically active metabolic enzyme PGM1. In the Atlantic herring, Clupea harengus, PGM5 is one of the genes strongly associated with ecological adaptation to the brackish Baltic Sea. We here present the first crystal structures of PGM5, from the Atlantic and Baltic herring, differing by a single substitution Ala330Val. The structure of PGM5 is overall highly similar to structures of PGM1. The structure of the Baltic herring PGM5 in complex with the substrate glucose-1-phosphate shows conserved substrate binding and active site compared to human PGM1, but both PGM5 variants lack phosphoglucomutase activity under the tested conditions. Structure comparison and sequence analysis of PGM5 and PGM1 from fish and mammals suggest that the lacking enzymatic activity of PGM5 is related to differences in active-site loops that are important for flipping of the reaction intermediate. The Ala330Val substitution does not alter structure or biophysical properties of PGM5 but, due to its surface-exposed location, could affect interactions with protein-binding partners.

Authors/Creators:Gustafsson, Robert and Eckhard, Ulrich and Ye, Weihua and Enbody, Erik D. and Pettersson, Mats and Jemth, Per and Andersson, Leif and Selmer, Maria
Title:Structure and Characterization of Phosphoglucomutase 5 from Atlantic and Baltic Herring-An Inactive Enzyme with Intact Substrate Binding
Series Name/Journal:Biomolecules
Year of publishing :2020
Volume:10
Article number:1631
Number of Pages:23
Publisher:MDPI
ISSN:2218-273X
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Biochemistry and Molecular Biology
Keywords:phosphoglucomutase 5, herring, adaptation, enzyme structure, phosphohexomutase
URN:NBN:urn:nbn:se:slu:epsilon-p-110203
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-110203
Additional ID:
Type of IDID
DOI10.3390/biom10121631
Web of Science (WoS)000602224300001
ID Code:21767
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
Deposited By: SLUpub Connector
Deposited On:27 Jan 2021 08:43
Metadata Last Modified:27 Jan 2021 08:51

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