Martin HögbomProfessor in Biochemistry
Research
Structural Biochemistry
Our main area of interest and expertise is how protein structure relates to function, in particular in proteins that utilize redox active metal cofactors or radicals for catalysis.
A central theme of our research is to obtain structural information of high-valent protein-coordinated metal sites used for extremely challenging chemical reactions. This information is central for the design of novel bioimetic catalysts for green chemistry and energy conversion. We also study the unique respiratory systems in Mycobacteria to characterize their structure and function. Energy metabolism in these pathogens is currently emerging as a promising new drug target.
We use tools such as synchrotron and free-electron laser X-ray crystallography, Cryo-EM, protein design, enzymatic assays and a variety of spectroscopic techniques.
Group members
Dan Sjöstrand, Researcher
Esra Bozkurt, Postdoc
Kristine Grave, Postdoc
Terezia Kovalova, Postdoc
Rohit Kumar, Postdoc
Soni Sharma, Postdoc
Vivek Srinivas, Postdoc
Niklas Segerström, Research assistant
Riccardo Diamanti, PhD Student
Juliane John, PhD Student
Representative Publications
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Wiseman B, Nitharwal RG, Widmalm G & Högbom M.
Structure of a full-length bacterial polysaccharide co-polymerase
Nature Communications, 2021, DOI: 10.1038/s41467-020-20579-1 -
Srinivas V, Banerjee R, Lebrette H, Jones JC, Aurelius O, Kim IS, Pham CC, Gul S, Sutherlin K, Bhowmick A, John J, Bozkurt E, Fransson T, Aller P, Butryn A, Bogacz I, Simon PS, Keable S, Britz A, Tono K, Kim KS, Park SY, Lee SJ, Park J, Alonso-Mori R, Fuller F, Batyuk A, Brewster A, Bergmann U, Sauter N, Orville AM, Yachandra VK, Yano J, Lipscomb JD, Kern JF & Högbom M
High Resolution XFEL Structure of the Soluble Methane Monooxygenase Hydroxylase Complex with its Regulatory Component at Ambient Temperature in Two Oxidation States.
J Am Chem Soc, 2020, Aug 142(33):14249-14266 -
Xu H, Lebrette H, Clabbers MTB, Zhao J, Griese JJ, Zou X & Högbom M.
Solving a new R2lox protein structure by microcrystal electron diffraction.
Science Advances, 2019, Aug 7;5(8):eaax4621 -
GrāveK, Bennett M & Högbom M.
Structure of Mycobacterium tuberculosis phosphatidylinositol phosphate synthase reveals mechanism of substrate binding and metal catalysis.
Communications Biology, 2019 May 8;2:175. -
Wiseman B, Nitharwal RG, Fedotovskaya O, Schäfer J, Guo H, Kuang Q, Benlekbir S, Sjöstrand D, Ädelroth P, Rubinstein JL, Brzezinski P & Högbom M.
Structure of a functional obligate complex III2IV2 respiratory supercomplex from Mycobacterium smegmatis
Nature Structural and Molecular Biology, 2018, Dec;25(12):1128-1136 -
Srinivas V, Lebrette H, Lundin D, Kutin Y, Sahlin M, Lerche M, Eirich J, Branca RMM, Cox N, Sjöberg B-M & Högbom M.
Metal-free ribonucleotide reduction powered by a DOPA radical in Mycoplasma pathogens
Nature, 2018, Nov;563(7731):416-420.
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Lundgren CAK, Sjöstrand D, Biner O, Bennett M, Rudling A, Johansson A-L, Brzezinski P, Carlsson J, von Ballmoos C & Högbom M.
Scavenging of superoxide by a membrane-bound superoxide oxidase
Nature Chemical Biology, 2018, Aug;14(8):788-793 -
Maugeri PT, Griese JJ, Branca RM, Miller EK, Smith ZR, Eirich J, Högbom M & Shafaat HS.
Driving Protein Conformational Changes with Light: Photoinduced Structural Rearrangement in a Heterobimetallic Oxidase
J Am Chem Soc, 2018, Jan 31;140(4):1471-14800
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Fuller FD et al.
Drop-on-demand sample delivery for studying biocatalysts in action at X-ray free-electron lasers
Nature Methods, 2017, Apr;14(4):443-449
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Griese JJ, Kositzki R, Schrapers P, Branca RM, Nordström A, Lehtiö J, Haumann M & Högbom M.
Structural Basis for Oxygen Activation at a Heterodinuclear Manganese/Iron Cofactor
J Biol Chem, 2015, Oct 16;290(42):25254-72 -
Högbom M.
Nitrogenase Mechanism. A dynamic tool for nitrogen reduction
Science, 2014, Sep 26;345(6204):1568 (perspective) -
Shafaat HS, Griese JJ, Pantazis DA, Roos K, Andersson CS, Popović-Bijelić A, Gräslund A, Siegbahn PE, Neese F, Lubitz W, Högbom M & Cox N.
Electronic structural flexibility of heterobimetallic Mn/Fe cofactors: R2lox and R2c proteins.
J Am Chem Soc, 2014, Sep 24;136(38):13399-409 -
Griese JJ, Roos K, Cox N, Shafaat HS, Branca RM, Lehtiö J, Gräslund A, Lubitz W, Siegbahn PE & Högbom M.
Direct observation of structurally encoded metal discrimination and ether bond formation in a heterodinuclear metalloprotein.
Proc Natl Acad Sci U S A, 2013 Oct 22;110(43):17189-94 -
Rollauer SE, Tarry MJ, Graham JE, Jääskeläinen M, Jäger F, Johnson S, Krehenbrink M, Liu SM, Lukey MJ, Marcoux J, McDowell MA, Rodriguez F, Roversi P, Stansfeld PJ, Robinson CV, Sansom MS, Palmer T, Högbom M, Berks BC & Lea SM.
Structure of the TatC core of the twin-arginine protein transport system.
Nature, 2012, 13;492(7428):210-4 -
Andersson CS, Lundgren CA, Magnúsdóttir A, Ge C, Wieslander A, Martinez Molina D & Högbom M.
The Mycobacterium tuberculosis very-long-chain fatty acyl-CoA synthetase: structural basis for housing lipid substrates longer than the enzyme.
Structure, 2012, 6;20(6):1062-70 -
Andersson CS, Öhrström M, Popović-Bijelić A, Gräslund A, Stenmark P & Högbom M.
The manganese ion of the heterodinuclear Mn/Fe cofactor in Chlamydia trachomatis ribonucleotide reductase R2c is located at metal position 1.
J Am Chem Soc, 2012, 11;134(1):123-5
Funding
