Structural and functional characterization of a lytic polysaccharide monooxygenase with broad substrate specificity

Anna S. Borisova, Trine Isaksen, Maria Dimarogona, Abhishek A. Kognole, Geir Mathiesen, Anikó Várnai, Åsmund K. Røhr, Christina M. Payne, Morten Sørlie, Mats Sandgren, Vincent G.H. Eijsink

Research output: Contribution to journalArticleScientificpeer-review

161 Citations (Scopus)


The recently discovered lytic polysaccharide monooxygenases (LPMOs) carry out oxidative cleavage of polysaccharides and are of major importance for efficient processing of biomass. NcLPMO9C from Neurospora crassa acts both on cellulose and on non-celluloseβ-glucans, including cellodextrins and xyloglucan. The crystal structure of the catalytic domain of NcLPMO9C revealed an extended, highly polar substrate-binding surface well suited to interact with a variety of sugar substrates. The ability of NcLPMO9C to act on soluble substrates was exploited to study enzyme-substrate interactions. EPR studies demonstrated that the Cu2+ center environment is altered upon substrate binding, whereas isothermal titration calorimetry studies revealed binding affinities in the low micromolar range for polymeric substrates that are due in part to the presence of a carbohydrate-binding module (CBM1). Importantly, the novel structure of NcLPMO9Cenabled a comparative study, revealing that the oxidative regioselectivity of LPMO9s (C1, C4, or both) correlates with distinct structural features of the copper coordination sphere. In strictly C1-oxidizing LPMO9s, access to the solvent-facing axial coordination position is restricted by a conserved tyrosine residue, whereas access to this same position seems unrestricted in C4-oxidizing LPMO9s. LPMO9s known to produce a mixture of C1- and C4-oxidized products show an intermediate situation.

Original languageEnglish
Pages (from-to)22955-22969
Number of pages15
JournalJournal of Biological Chemistry
Issue number38
Publication statusPublished - 18 Sept 2015
MoE publication typeA1 Journal article-refereed


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