Role of Cys73 in the thermostability of farnesyl diphosphate synthase from Geobacillus stearothermophilus

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Abstract

Farnesyl diphosphate synthase (FPPase) is an enzyme that catalyzes the condensation between one molecule of dimethylallyl diphosphate (DMAPP) and two molecules of isopentenyl diphosphate (IPP) to produce farnesyl diphosphate (FPP). FPP is an important precursor in the isoprenoid synthesis pathway. In this study, the crystal structure of FPPase from Geobacillus stearothermophilus ( GsFPPase) was determined at 2.31 Å resolution. The structure of GsFPPase shows a three-layered all α-helical fold and conserved functional domains similar to other prenyltransferases. We have analyzed the structural features of GsFPPase related to thermostability and compared it with those of human and avian mesophilic FPPases. “Semi-conserved” regions which appear to be possible features contributing to the thermostability of FPPase were found.

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Most cited references 21

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Protein rigidity and thermophilic adaptation.

Sebastian Radestock, Holger Gohlke (2011)

We probe the hypothesis of corresponding states, according to which homologues from mesophilic and thermophilic organisms are in corresponding states of similar rigidity and flexibility at their respective optimal temperatures. For this, the local distribution of flexible and rigid regions in 19 pairs of homologous proteins from meso- and thermophilic organisms is analyzed and related to activity characteristics of the enzymes by constraint network analysis (CNA). Two pairs of enzymes are considered in more detail: 3-isopropylmalate dehydrogenase and thermolysin-like protease. By comparing microscopic stability features of homologues with the help of stability maps, introduced for the first time, we show that adaptive mutations in enzymes from thermophilic organisms maintain the balance between overall rigidity, important for thermostability, and local flexibility, important for activity, at the appropriate working temperature. Thermophilic adaptation in general leads to an increase of structural rigidity but conserves the distribution of functionally important flexible regions between homologues. This finding provides direct evidence for the hypothesis of corresponding states. CNA thereby implicitly captures and unifies many different mechanisms that contribute to increased thermostability and to activity at high temperatures. This allows to qualitatively relate changes in the flexibility of active site regions, induced either by a temperature change or by the introduction of mutations, to experimentally observed losses of the enzyme function. As for applications, the results demonstrate that exploiting the principle of corresponding states not only allows for successful thermostability optimization but also for guiding experiments in order to improve enzyme activity in protein engineering. Copyright © 2010 Wiley-Liss, Inc.

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Enzymatic Aspects of Isoprenoid Chain Elongation.

K. Ogura, T. Koyama (1998)

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Isoprenyl diphosphate synthases: protein sequence comparisons, a phylogenetic tree, and predictions of secondary structure.

A. Chen, P A Kroon, C D Poulter (1994)

Isoprenyl diphosphate synthases are ubiquitous enzymes that catalyze the basic chain-elongation reaction in the isoprene biosynthetic pathway. Pairwise sequence comparisons were made for 6 farnesyl diphosphate synthases, 6 geranylgeranyl diphosphate synthases, and a hexaprenyl diphosphate synthase. Five regions with highly conserved residues, two of which contain aspartate-rich DDXX(XX)D motifs found in many prenyltransferases, were identified. A consensus secondary structure for the group, consisting mostly of alpha-helices, was predicted for the multiply aligned sequences from amino acid compositions, computer assignments of local structure, and hydropathy indices. Progressive sequence alignments suggest that the 13 isoprenyl diphosphate synthases evolved from a common ancestor into 3 distinct clusters. The most distant separation is between yeast hexaprenyl diphosphate synthetase and the other enzymes. Except for the chromoplastic geranylgeranyl diphosphate synthase from Capsicum annuum, the remaining farnesyl and geranylgeranyl diphosphate synthases segregate into prokaryotic/archaebacterial and eukaryotic families.

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Author and article information

Contributors

Tatsuro Kijima:

ORCID: http://orcid.org/0000-0002-9741-5266

kijima@yz.yamagata-u.ac.jp

Journal

Journal ID (nlm-ta): 3 Biotech

Journal ID (iso-abbrev): 3 Biotech

Title: 3 Biotech

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 2190-572X

ISSN (Electronic): 2190-5738

Publication date (Electronic): 10 July 2017

Publication date PMC-release: 10 July 2017

Publication date (Print): August 2017

Volume: 7

Issue: 4

Electronic Location Identifier: 236

Affiliations

[1 ]ISNI 0000 0001 0674 7277, GRID grid.268394.2, Department of Biochemical Engineering, Graduate School of Science and Engineering, , Yamagata University, ; 4-3-16 Jonan, Yonezawa, Yamagata 992-8510 Japan

[2 ]ISNI 0000 0001 0674 7277, GRID grid.268394.2, Department of Material and Biological Chemistry, Faculty of Science, , Yamagata University, ; 1-4-12 Kojirakawa, Yamagata, Yamagata 990-8560 Japan

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Tatsuro Kijima http://orcid.org/0000-0002-9741-5266

Article

Publisher ID: 792

DOI: 10.1007/s13205-017-0792-8

PMC ID: 5503844

SO-VID: 4f9e167c-98c5-4eca-ba07-3de0f9ff56a3

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 13 May 2017

Date accepted : 14 June 2017

Funding

Funded by: Sasakawa Scientific Research Grant from The Japan Science Society

Award ID: 28-328

Award Recipient : Petrus Yesaya Samori

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Keywords: farnesyl diphosphate synthase,geobacillus stearothermophilus,thermostability,crystal structure,thermal unfolding simulation

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Keywords: farnesyl diphosphate synthase, geobacillus stearothermophilus, thermostability, crystal structure, thermal unfolding simulation

Role of Cys73 in the thermostability of farnesyl diphosphate synthase from Geobacillus stearothermophilus

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Most cited references 21

Protein rigidity and thermophilic adaptation.

Enzymatic Aspects of Isoprenoid Chain Elongation.

Isoprenyl diphosphate synthases: protein sequence comparisons, a phylogenetic tree, and predictions of secondary structure.

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