Impaired folate binding of serine hydroxymethyltransferase 8 from soybean underlies resistance to the soybean cyst nematode

Korasick, David A.; Kandoth, Pramod K.; Tanner, John J.; Mitchum, Melissa G.; Beamer, Lesa J.

doi:10.1074/jbc.RA119.012256

Impaired folate binding of serine hydroxymethyltransferase 8 from soybean underlies resistance to the soybean cyst nematode

Journal Article · Sun Feb 02 00:00:00 EST 2020 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.RA119.012256· OSTI ID:1616596

^[1]; Kandoth, Pramod K. ^[1]; ^[1]; ^[1]; ^[1]

Univ. of Missouri, Columbia, MO (United States)

Management of the agricultural pathogen soybean cyst nematode (SCN) relies on the use of SCN-resistant soybean cultivars, a strategy that has been failing in recent years. An underutilized source of resistance in the soybean genotype Peking is linked to two polymorphisms in serine hydroxy-methyltransferase 8 (SHMT8). SHMT is a pyridoxal 5'-phosphate–dependent enzyme that converts L-serine and (6S)-tetrahydrofolate to glycine and 5,10-methylenetetrahydrofolate. In this work, we determined five crystal structures of the 1884-residue SHMT8 tetramers from the SCN-susceptible cultivar (cv.) Essex and the SCN-resistant cv. Forrest (whose resistance is derived from the SHMT8 polymorphisms in Peking); the crystal structures were determined in complex with various ligands at 1.4–2.35 Å resolutions. We find that the two Forrest-specific polymorphic substitutions (P130R and N358Y) impact the mobility of a loop near the entrance of the (6S)-tetrahydrofolate–binding site. Ligand-binding and kinetic studies indicate severely reduced affinity for folate and dramatically impaired enzyme activity in Forrest SHMT8. These findings imply widespread effects on folate metabolism in soybean cv. Forrest that have implications for combating the widespread increase in virulent SCN.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Advanced Light Source (ALS

Sponsoring Organization:: Missouri Soybean Mercchanising Council; National Institute of Food and Agriculture (NIFA); National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDA; USDOE Office of Science (SC); University of Missouri Bond Life Sciences Center

Grant/Contract Number:: AC02-05CH11231; AC02-06CH11357

OSTI ID:: 1616596

Alternate ID(s):: OSTI ID: 1767199

Journal Information:: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 11 Vol. 295; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (46)

Conformational Aspects in the Design of Inhibitors for Serine Hydroxymethyltransferase (SHMT): Biphenyl, Aryl Sulfonamide, and Aryl Sulfone Motifs Schwertz, Geoffrey; Frei, Michelle S.; Witschel, Matthias C. Chemistry - A European Journal, Vol. 23, Issue 57 https://doi.org/10.1002/chem.201703244	journal	October 2017
Potent Inhibitors of Plasmodial Serine Hydroxymethyltransferase (SHMT) Featuring a Spirocyclic Scaffold Schwertz, Geoffrey; Witschel, Matthias C.; Rottmann, Matthias ChemMedChem, Vol. 13, Issue 9 https://doi.org/10.1002/cmdc.201800053	journal	April 2018
Crystal structure at 2.4 Å resolution of E. coli serine hydroxymethyltransferase in complex with glycine substrate and 5-formyl tetrahydrofolate 1 1Edited by I. A. Wilson Scarsdale, J. Neel; Radaev, S.; Kazanina, G. Journal of Molecular Biology, Vol. 296, Issue 1 https://doi.org/10.1006/jmbi.1999.3453	journal	February 2000
Automated Structure Solution with the PHENIX Suite Zwart, Peter H.; Afonine, Pavel V.; Grosse-Kunstleve, Ralf W. Methods in Molecular Biology https://doi.org/10.1007/978-1-60327-058-8_28	book	January 2008
Graphical determination of the dissociation constants for two-substrate enzyme systems Florini, James R.; Vestling, Carl S. Biochimica et Biophysica Acta, Vol. 25 https://doi.org/10.1016/0006-3002(57)90529-2	journal	January 1957
Folate polyglutamylation eliminates dependence of activity on enzyme concentration in mitochondrial serine hydroxymethyltransferases from Arabidopsis thaliana Wei, Zhaoyang; Sun, Kehan; Sandoval, Francisco J. Archives of Biochemistry and Biophysics, Vol. 536, Issue 1 https://doi.org/10.1016/j.abb.2013.06.004	journal	August 2013
Impact of Mutating the Key Residues of a Bifunctional 5,10-Methylenetetrahydrofolate Dehydrogenase-Cyclohydrolase from Escherichia coli on Its Activities Sah, Shivjee; Varshney, Umesh Biochemistry, Vol. 54, Issue 22 https://doi.org/10.1021/acs.biochem.5b00400	journal	May 2015
Human Cytosolic and Mitochondrial Serine Hydroxymethyltransferase Isoforms in Comparison: Full Kinetic Characterization and Substrate Inhibition Properties Tramonti, Angela; Nardella, Caterina; di Salvo, Martino L. Biochemistry, Vol. 57, Issue 51 https://doi.org/10.1021/acs.biochem.8b01074	journal	November 2018
Antimalarial Inhibitors Targeting Serine Hydroxymethyltransferase (SHMT) with in Vivo Efficacy and Analysis of their Binding Mode Based on X-ray Cocrystal Structures Schwertz, Geoffrey; Witschel, Matthias C.; Rottmann, Matthias Journal of Medicinal Chemistry, Vol. 60, Issue 12 https://doi.org/10.1021/acs.jmedchem.7b00008	journal	June 2017
Role of Tyrosine 65 in the Mechanism of Serine Hydroxymethyltransferase ^† Contestabile, Roberto; Angelaccio, Sebastiana; Bossa, Francesco Biochemistry, Vol. 39, Issue 25 https://doi.org/10.1021/bi000032z	journal	June 2000
Structure of a Murine Cytoplasmic Serine Hydroxymethyltransferase Quinonoid Ternary Complex: Evidence for Asymmetric Obligate Dimers ^† Szebenyi, Doletha M. E.; Liu, Xiaowen; Kriksunov, Irina A. Biochemistry, Vol. 39, Issue 44 https://doi.org/10.1021/bi000635a	journal	November 2000
Purification and characterization of pyridoxal 5'-phosphate dependent serine hydroxymethylase from lamb liver and its action upon β-phenylserines Ulevitch, Richard J.; Kallen, Roland G. Biochemistry, Vol. 16, Issue 24 https://doi.org/10.1021/bi00643a027	journal	November 1977
Serine Transhydroxymethylase. Affinity of Tetrahydrofolate Compounds for the Enzyme and Enzyme-Glycine Complex ^* Schirch, LaVerne; Ropp, Marjorie Biochemistry, Vol. 6, Issue 1 https://doi.org/10.1021/bi00853a039	journal	January 1967
Inhibitors of Plasmodial Serine Hydroxymethyltransferase (SHMT): Cocrystal Structures of Pyrazolopyrans with Potent Blood- and Liver-Stage Activities Witschel, Matthias C.; Rottmann, Matthias; Schwab, Anatol Journal of Medicinal Chemistry, Vol. 58, Issue 7 https://doi.org/10.1021/jm501987h	journal	March 2015
SHMT1 knockdown induces apoptosis in lung cancer cells by causing uracil misincorporation Paone, A.; Marani, M.; Fiascarelli, A. Cell Death & Disease, Vol. 5, Issue 11 https://doi.org/10.1038/cddis.2014.482	journal	November 2014
A soybean cyst nematode resistance gene points to a new mechanism of plant resistance to pathogens Liu, Shiming; Kandoth, Pramod K.; Warren, Samantha D. Nature, Vol. 492, Issue 7428 https://doi.org/10.1038/nature11651	journal	October 2012
Design strategy for serine hydroxymethyltransferase probes based on retro-aldol-type reaction Nonaka, Hiroshi; Nakanishi, Yuki; Kuno, Satoshi Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-08833-7	journal	February 2019
Genome reorganization of the GmSHMT gene family in soybean showed a lack of functional redundancy in resistance to soybean cyst nematode Lakhssassi, Naoufal; Patil, Gunvant; Piya, Sarbottam Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-018-37815-w	journal	February 2019
Structural basis of methotrexate and pemetrexed action on serine hydroxymethyltransferases revealed using plant models Ruszkowski, Milosz; Sekula, Bartosz; Ruszkowska, Agnieszka Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-56043-4	journal	December 2019
Structural and functional studies of Bacillus stearothermophilus serine hydroxymethyltransferase: the role of Asn341, Tyr60 and Phe351 in tetrahydrofolate binding Pai, Vinitha R.; Rajaram, V.; Bisht, Shveta Biochemical Journal, Vol. 418, Issue 3 https://doi.org/10.1042/BJ20081739	journal	February 2009
Human SHMT inhibitors reveal defective glycine import as a targetable metabolic vulnerability of diffuse large B-cell lymphoma Ducker, Gregory S.; Ghergurovich, Jonathan M.; Mainolfi, Nello Proceedings of the National Academy of Sciences, Vol. 114, Issue 43 https://doi.org/10.1073/pnas.1706617114	journal	October 2017
Crystal Structure of Binary and Ternary Complexes of Serine Hydroxymethyltransferase from Bacillus stearothermophilus: INSIGHTS INTO THE CATALYTIC MECHANISM Trivedi, V.; Gupta, A.; Jala, V. R. Journal of Biological Chemistry, Vol. 277, Issue 19 https://doi.org/10.1074/jbc.M111976200	journal	May 2002
Location of the Pteroylpolyglutamate-binding Site on Rabbit Cytosolic Serine Hydroxymethyltransferase Fu, Tzu-Fun; Scarsdale, J. Neel; Kazanina, Galina Journal of Biological Chemistry, Vol. 278, Issue 4 https://doi.org/10.1074/jbc.M210649200	journal	November 2002
A flap motif in human serine hydroxymethyltransferase is important for structural stabilization, ligand binding, and control of product release Ubonprasert, Sakunrat; Jaroensuk, Juthamas; Pornthanakasem, Wichai Journal of Biological Chemistry, Vol. 294, Issue 27 https://doi.org/10.1074/jbc.RA119.007454	journal	May 2019
A fully automatic evolutionary classification of protein folds: Dali Domain Dictionary version 3 Dietmann, S. Nucleic Acids Research, Vol. 29, Issue 1 https://doi.org/10.1093/nar/29.1.55	journal	January 2001
Increase in Soybean Cyst Nematode Virulence and Reproduction on Resistant Soybean Varieties in Iowa From 2001 to 2015 and the Effects on Soybean Yields McCarville, Michael T.; Marett, Christopher C.; Mullaney, Mark P. Plant Health Progress, Vol. 18, Issue 3 https://doi.org/10.1094/PHP-RS-16-0062	journal	January 2017
Soybean Yield Loss Estimates Due to Diseases in the United States and Ontario, Canada, from 2010 to 2014 Allen, Tom W.; Bradley, Carl A.; Sisson, Adam J. Plant Health Progress, Vol. 18, Issue 1 https://doi.org/10.1094/PHP-RS-16-0066	journal	January 2017
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
Integration, scaling, space-group assignment and post-refinement Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 133-144 https://doi.org/10.1107/S0907444909047374	journal	January 2010
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
How good are my data and what is the resolution? Evans, Philip R.; Murshudov, Garib N. Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 7 https://doi.org/10.1107/S0907444913000061	journal	June 2013
Structures of Plasmodium vivax serine hydroxymethyltransferase: implications for ligand-binding specificity and functional control Chitnumsub, Penchit; Jaruwat, Aritsara; Riangrungroj, Pinpunya Acta Crystallographica Section D Biological Crystallography, Vol. 70, Issue 12 https://doi.org/10.1107/S1399004714023128	journal	November 2014
Distinct biochemical properties of human serine hydroxymethyltransferase compared with the Plasmodium enzyme: implications for selective inhibition Pinthong, Chatchadaporn; Maenpuen, Somchart; Amornwatcharapong, Watcharee FEBS Journal, Vol. 281, Issue 11 https://doi.org/10.1111/febs.12803	journal	April 2014
The catalytic activity of serine hydroxymethyltransferase is essential for de novo nuclear dTMP synthesis in lung cancer cells Giardina, Giorgio; Paone, Alessio; Tramonti, Angela The FEBS Journal, Vol. 285, Issue 17 https://doi.org/10.1111/febs.14610	journal	June 2018
Functional analysis of folate polyglutamylation and its essential role in plant metabolism and development Mehrshahi, Payam; Gonzalez-Jorge, Sabrina; Akhtar, Tariq A. The Plant Journal, Vol. 64, Issue 2, p. 267-279 https://doi.org/10.1111/j.1365-313X.2010.04336.x	journal	September 2010
Mechanism for folate-independent aldolase reaction catalyzed by serine hydroxymethyltransferase: Y. Chiba et al. Chiba, Yoko; Terada, Tohru; Kameya, Masafumi FEBS Journal, Vol. 279, Issue 3 https://doi.org/10.1111/j.1742-4658.2011.08443.x	journal	December 2011
Whole-genome re-sequencing reveals the impact of the interaction of copy number variants of the rhg1 and Rhg4 genes on broad-based resistance to soybean cyst nematode Patil, Gunvant B.; Lakhssassi, Naoufal; Wan, Jinrong Plant Biotechnology Journal, Vol. 17, Issue 8 https://doi.org/10.1111/pbi.13086	journal	February 2019
Metabolite Profiling Identifies a Key Role for Glycine in Rapid Cancer Cell Proliferation Jain, M.; Nilsson, R.; Sharma, S. Science, Vol. 336, Issue 6084 https://doi.org/10.1126/science.1218595	journal	May 2012
Copy Number Variation of Multiple Genes at Rhg1 Mediates Nematode Resistance in Soybean Cook, D. E.; Lee, T. G.; Guo, X. Science, Vol. 338, Issue 6111 https://doi.org/10.1126/science.1228746	journal	October 2012
The Activation and Suppression of Plant Innate Immunity by Parasitic Nematodes Goverse, Aska; Smant, Geert Annual Review of Phytopathology, Vol. 52, Issue 1 https://doi.org/10.1146/annurev-phyto-102313-050118	journal	August 2014
Soybean Genomics: Developments through the Use of Cultivar “Forrest” Lightfoot, David A. International Journal of Plant Genomics, Vol. 2008 https://doi.org/10.1155/2008/793158	journal	January 2008
Plasmodium serine hydroxymethyltransferase as a potential anti-malarial target: inhibition studies using improved methods for enzyme production and assay Sopitthummakhun, Kittipat; Thongpanchang, Chawanee; Vilaivan, Tirayut Malaria Journal, Vol. 11, Issue 1 https://doi.org/10.1186/1475-2875-11-194	journal	January 2012
Registration of ‘Forrest’ Soybeans ¹ (Reg. No. 96) Hartwig, E. E.; Epps, J. M. Crop Science, Vol. 13, Issue 2 https://doi.org/10.2135/cropsci1973.0011183X001300020047x	journal	March 1973
Soybean Cyst Nematode Resistance Emerged via Artificial Selection of Duplicated Serine Hydroxymethyltransferase Genes Wu, Xiao-Yi; Zhou, Guang-Can; Chen, Yun-Xia Frontiers in Plant Science, Vol. 7 https://doi.org/10.3389/fpls.2016.00998	journal	July 2016
Chloroplastic Serine Hydroxymethyltransferase From Medicago truncatula: A Structural Characterization Ruszkowski, Milosz; Sekula, Bartosz; Ruszkowska, Agnieszka Frontiers in Plant Science, Vol. 9 https://doi.org/10.3389/fpls.2018.00584	journal	May 2018

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
Glycine max
X-ray crystallography
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plant defense
quantitative trait loci (QTL)
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Impaired folate binding of serine hydroxymethyltransferase 8 from soybean underlies resistance to the soybean cyst nematode

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References (46)

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