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Gunter Schneider group

Research at the division of Molecular Structural Biology and the Gunter Schneider research group covers a broad range of topics, from structural enzymology, infection biology to molecular neurobiology and development of soft- and hardware for macromolecular crystallography.

Research at the division is supported by Karolinska Institutet, the Swedish Science Council (VR), and VINNOVA.

Research projects

Structural enzymology of the biosynthesis of polyketide antibiotics

Anthracyclines are secondary metabolites of Streptomyces, and members of this class of polyketide antibiotics belong to the most-used chemotherapeutic agents in the combat against cancer. The research program aims at the elucidation of the structural enzymology of anthracycline biosynthesis. Target selection is focused on enzymes not related in sequence to proteins of known structure, and/or novel enzymatic mechanisms.

The project is lead by Gunter Schneider.

Structural biology of bacterial pathogens

This research project aims at the structural and functional characterization of proteins and protein complexes from major pathogens, in particular Gram–negative bacteria and Mycobacterium tuberculosis. One of the objectives of this program is to provide sufficient structural and mechanistic insights to facilitate the design of strong binding inhibitors, which may be developed into novel drugs.

The project is lead by Gunter Schneider and Robert Schnell.

Development of soft- and hardware for macromolecular crystallography

For more information, see Lohkamp group.

Structures

Here a selection of structures solved in our lab. A complete list is available at the Protein Data Bank.

SnoK/N couple

5EPA, 5EQU, 5ERL, 5EP9

Divergent non-heme iron enzymes in the nogalamycin biosynthetic pathway.
Siitonen V, Selvaraj B, Niiranen L, Lindqvist Y, Schneider G, Metsä-Ketelä M
Proc. Natl. Acad. Sci. U.S.A. 2016 May;113(19):5251-6

Arthritogenic Antibody-collagen complex

4BKL

Epitope-specific antibody response is controlled by immunoglobulin V(H) polymorphisms.
Raposo B, Dobritzsch D, Ge C, Ekman D, Xu B, Lindh I, et al
J. Exp. Med. 2014 Mar;211(3):405-11

SnoaL

1SJW

Structure of the polyketide cyclase SnoaL reveals a novel mechanism for enzymatic aldol condensation.
Sultana A, Kallio P, Jansson A, Wang JS, Niemi J, Mäntsälä P, et al
EMBO J. 2004 May;23(9):1911-21

Formyl-CoA Transferase (FRC)

1P5H, 1P5R, 1T3Z, 1VGR, 1VGQ, 2VGM, 2VGK, 2VGP

Formyl-CoA transferase encloses the CoA binding site at the interface of an interlocked dimer.
Ricagno S, Jonsson S, Richards N, Lindqvist Y
EMBO J. 2003 Jul;22(13):3210-9

Dihydropyrimidine Dehydrogenase

1H7X, 1H7W, 1GT8, 1GTE, 1GTH

Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil.
Dobritzsch D, Schneider G, Schnackerz KD, Lindqvist Y
EMBO J. 2001 Feb;20(4):650-60

Human Pro-Matrix Metalloproteinase-2 (Gelatinase A)

1CK7

Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed.
Morgunova E, Tuuttila A, Bergmann U, Isupov M, Lindqvist Y, Schneider G, et al
Science 1999 Jun;284(5420):1667-70

Ketoacyl ACP-synthase II

1E5M, 1B3N, 1KAS

Crystal structure of beta-ketoacyl-acyl carrier protein synthase II from E.coli reveals the molecular architecture of condensing enzymes.
Huang W, Jia J, Edwards P, Dehesh K, Schneider G, Lindqvist Y
EMBO J. 1998 Mar;17(5):1183-91

Nitrile hydratase

1AHJ

Crystal structure of nitrile hydratase reveals a novel iron centre in a novel fold.
Huang W, Jia J, Cummings J, Nelson M, Schneider G, Lindqvist Y
Structure 1997 May;5(5):691-9

Desaturase

1AFR, 1OQ4, 1OQ7, 1OQ9, 1OQB, 2J2F, 2UW1

Crystal structure of delta9 stearoyl-acyl carrier protein desaturase from castor seed and its relationship to other di-iron proteins.
Lindqvist Y, Huang W, Schneider G, Shanklin J
EMBO J. 1996 Aug;15(16):4081-92

Transketolase

1GPU, 1AYO , 1NGS, 1TRK, 1TKB, 1TKC, 1TKA, 1R9J

Three-dimensional structure of transketolase, a thiamine diphosphate dependent enzyme, at 2.5 A resolution.
Lindqvist Y, Schneider G, Ermler U, Sundström M
EMBO J. 1992 Jul;11(7):2373-9

Research group

Name Title
Victoria Balabanova Administratör
RESHMA RUDRARAJU Postdoc
Gunter Schneider Professor
Robert Schnell Forskare
Edit Szodorai Anknuten

Alumni: Postdocs

  • Ulrich Ermler
  • Matti Nikkola
  • Alokesh Ghoshal
  • Matthias Stehr
  • Susana Cristobal
  • Yuhuan Zheng
  • Alexei Dubrovsky
  • Philipp Beinker
  • Jishu Wang
  • Inari Kursula
  • Jean-Marie Bourhis
  • Mikko Metsä-Ketelä
  • Laura Silvennoinen
  • Jolanta Kopec
  • Agata Jacewicz
  • Atsushi Izumi
  • Rajesh Ponnusamy
  • Ekaterina Biterova
  • Jason Schmidberger
  • Cyprian Cukier
  • Doreen Dobritzsch
  • Jodie Guy
  • Ömer Poyraz
  • Selma Maric
  • Brinda Selvaraj
  • Francesca Abate
  • Shoude Zhang
  • Richard Tjörnhammer
  • Tatyana Sandalova

Alumni: PhD students

  • Tomas Lundqvist,1991
  • Michael Sundström, 1992
  • Guoguang Lu, 1994
  • Arnold Andersson, 1996
  • Weijun Huang, 1996
  • Jia Jia, 1996
  • Kaj Stenberg, 1997
  • Christer Wikner, 1997
  • Ulrika Nilsson, 1997
  • Cristoffer Enroth, 1998
  • Karina Persson, 1999
  • Helena Käck, 1999
  • Eva Johansson, 2000
  • Stina Thorell, 2001
  • Louise Kraft, 2001
  • Martin Moche, 2003
  • Jenny Sandmark, 2003
  • Anna Jansson, 2004
  • Lucas Malard Velloso, 2004
  • Stefano Ricagno, 2004
  • Azmiri Sultana, 2006
  • Catrine Berthold, 2008
  • Stina Lundgren, 2008
  • Daniel Ågren, 2009
  • Hanna Koskiniemi, 2009
  • Magnus Claesson, 2013
  • Maria Svärd, 2014
  • Ming Wei Chen, 2014
  • Dominic Böth, 2014
  • Edvard Wigren, 2012
  • Dominik Possner, 2016
  • Katharina Brunner, 2017

Selected publications

Inhibitors of the Cysteine Synthase CysM with Antibacterial Potency against Dormant Mycobacterium tuberculosis.
Brunner K, Maric S, Reshma RS, Almqvist H, Seashore-Ludlow B, Gustavsson AL, et al
J. Med. Chem. 2016 07;59(14):6848-59

Divergent non-heme iron enzymes in the nogalamycin biosynthetic pathway.
Siitonen V, Selvaraj B, Niiranen L, Lindqvist Y, Schneider G, Metsä-Ketelä M
Proc. Natl. Acad. Sci. U.S.A. 2016 May;113(19):5251-6

Epitope-specific antibody response is controlled by immunoglobulin V(H) polymorphisms.
Raposo B, Dobritzsch D, Ge C, Ekman D, Xu B, Lindh I, et al
J. Exp. Med. 2014 Mar;211(3):405-11

Discovery of an allosteric inhibitor binding site in 3-Oxo-acyl-ACP reductase from Pseudomonas aeruginosa.
Cukier CD, Hope AG, Elamin AA, Moynie L, Schnell R, Schach S, et al
ACS Chem. Biol. 2013 Nov;8(11):2518-27

Structure-guided design of novel thiazolidine inhibitors of O-acetyl serine sulfhydrylase from Mycobacterium tuberculosis.
Poyraz O, Jeankumar VU, Saxena S, Schnell R, Haraldsson M, Yogeeswari P, et al
J. Med. Chem. 2013 Aug;56(16):6457-66

Structural basis for C-ribosylation in the alnumycin A biosynthetic pathway.
Oja T, Niiranen L, Sandalova T, Klika KD, Niemi J, Mäntsälä P, et al
Proc. Natl. Acad. Sci. U.S.A. 2013 Jan;110(4):1291-6

Crystal structure of an arthritogenic anticollagen immune complex.
Dobritzsch D, Lindh I, Uysal H, Nandakumar KS, Burkhardt H, Schneider G, et al
Arthritis Rheum. 2011 Dec;63(12):3740-8

Features and development of Coot.
Emsley P, Lohkamp B, Scott WG, Cowtan K
Acta Crystallogr. D Biol. Crystallogr. 2010 Apr;66(Pt 4):486-501

Cysteine synthase (CysM) of Mycobacterium tuberculosis is an O-phosphoserine sulfhydrylase: evidence for an alternative cysteine biosynthesis pathway in mycobacteria.
Agren D, Schnell R, Oehlmann W, Singh M, Schneider G
J. Biol. Chem. 2008 Nov;283(46):31567-74

Aclacinomycin oxidoreductase (AknOx) from the biosynthetic pathway of the antibiotic aclacinomycin is an unusual flavoenzyme with a dual active site.
Alexeev I, Sultana A, Mäntsälä P, Niemi J, Schneider G
Proc. Natl. Acad. Sci. U.S.A. 2007 Apr;104(15):6170-5

Contact

Visiting address

Division of Molecular Structural Biology
Department of Medical Biochemistry and Biophysics
Karolinska Institutet
Biomedicum, 9D, floor 9
171 65 Solna
Sweden

Phone (secretary): +46 8 524 8 7676
Fax: +46 8 327626