Martin Moche's Publications List

Combined x-ray crystallography and computational modeling approach to investigate the Hsp90 C-terminal peptide binding to FKBP51.

2017-12-30T21:17:39Z

FK506 binding protein of 51 kDa (FKBP51) is a heat shock protein 90 (Hsp90) co-chaperone involved in the regulation of steroid hormone receptors activity. It is known for its role in various regulatory pathways implicated in mood and stress-related disorders, cancer, obesity, Alzheimer's disease and corticosteroid resistant asthma. It consists of two FKBP12 like active peptidyl prolyl isomerase ...

Rajnish Kumar, Martin Moche, Bengt Winblad, Pavel F Pavlov (2017) Scientific reports 7: 1

Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.

2017-12-30T21:17:39Z

Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitors and commonly used research tools for their inhibition of multiple PARP enzymes. We also determined crystal structures of these compounds bound to PARP1 or PARP2. Veliparib and niraparib are selective i...

Ann-Gerd Thorsell, Torun Ekblad, Tobias Karlberg, Mirjam Löw, Ana Filipa Pinto, Lionel Trésaugues, Martin Moche, Michael S Cohen, Herwig Schüler (2017) Journal of medicinal chemistry 60: 4 1262-1271

Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression.

2017-12-30T21:17:39Z

MexR is a repressor of the MexAB-OprM multidrug efflux pump operon of Pseudomonas aeruginosa, where DNA-binding impairing mutations lead to multidrug resistance (MDR). Surprisingly, the crystal structure of an MDR-conferring MexR mutant R21W (2.19 Å) presented here is closely similar to wild-type MexR. However, our extended analysis, by molecular dynamics and small-angle X-ray scattering, reveal...

Madhanagopal Anandapadamanaban, Robert Pilstål, Cecilia Andresen, Jill Trewhella, Martin Moche, Björn Wallner, Maria Sunnerhagen (2016) Structure (London, England : 1993) 24: 8 1311-1321

Half-of-the-Sites Reactivity of the Castor Δ9-18:0-Acyl Carrier Protein Desaturase.

2015-12-15T11:38:23Z

Fatty acid desaturases regulate the unsaturation status of cellular lipids. They comprise two distinct evolutionary lineages, a soluble class found in the plastids of higher plants and an integral membrane class found in plants, yeast (Saccharomyces cerevisiae), animals, and bacteria. Both classes exhibit a dimeric quaternary structure. Here, we test the functional significance of dimeric organiza...

Qin Liu, Jin Chai, Martin Moche, Jodie Guy, Ylva Lindqvist, John Shanklin (2015) Plant physiology 169: 1 432-441

High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation.

2013-07-24T23:03:14Z

The general transcription factor TFIID provides a regulatory platform for transcription initiation. Here we present the crystal structure (1.97 Å) and NMR analysis of yeast TAF1 N-terminal domains TAND1 and TAND2 bound to yeast TBP, together with mutational data. We find that yeast TAF1-TAND1, which in itself acts as a transcriptional activator, binds TBP's concave DNA-binding surface by presenti...

Madhanagopal Anandapadamanaban, Cecilia Andresen, Sara Helander, Yoshifumi Ohyama, Marina I Siponen, Patrik Lundström, Tetsuro Kokubo, Mitsuhiko Ikura, Martin Moche, Maria Sunnerhagen (2013) Nature structural & molecular biology :

Enzymatic production of 'monoclonal stoichiometric' single-stranded DNA oligonucleotides.

2013-07-24T23:06:20Z

Single-stranded oligonucleotides are important as research tools, as diagnostic probes, in gene therapy and in DNA nanotechnology. Oligonucleotides are typically produced via solid-phase synthesis, using polymer chemistries that are limited relative to what biological systems produce. The number of errors in synthetic DNA increases with oligonucleotide length, and the resulting diversity of sequen...

Cosimo Ducani, Corinna Kaul, Martin Moche, William M Shih, Björn Högberg (2013) Nature methods 10: 7 647-52

Remote control of regioselectivity in acyl-acyl carrier protein-desaturases.

2012-11-10T21:28:27Z

Regiospecific desaturation of long-chain saturated fatty acids has been described as approaching the limits of the discriminatory power of enzymes because the substrate entirely lacks distinguishing features close to the site of dehydrogenation. To identify the elusive mechanism underlying regioselectivity, we have determined two crystal structures of the archetypal Δ9 desaturase from castor in c...

Jodie E Guy, Edward Whittle, Martin Moche, Johan Lengqvist, Ylva Lindqvist, John Shanklin (2011) Proc Natl Acad Sci U S A 108: 40 16594-16599

Crystal structures of the ATPase domains of four human Hsp70 isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and HSPA5/BiP/GRP78.

2010-04-28T13:23:00Z

The 70-kDa heat shock proteins (Hsp70) are chaperones with central roles in processes that involve polypeptide remodeling events. Hsp70 proteins consist of two major functional domains: an N-terminal nucleotide binding domain (NBD) with ATPase activity, and a C-terminal substrate binding domain (SBD). We present the first crystal structures of four human Hsp70 isoforms, those of the NBDs of HSPA1L...

Magdalena Wisniewska, Tobias Karlberg, Lari Lehtiö, Ida Johansson, Tetyana Kotenyova, Martin Moche, Herwig Schüler (2010) PLoS One 5: 1

Comparative structural analysis of human DEAD-box RNA helicases.

2010-11-13T20:57:04Z

DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA rem...

Patrick Schütz, Tobias Karlberg, Susanne van den Berg, Ruairi Collins, Lari Lehtiö, Martin Högbom, Lovisa Holmberg-Schiavone, Wolfram Tempel, Hee-Won Park, Martin Hammarström, Martin Moche, Ann-Gerd Thorsell, Herwig Schüler (2010) PLoS One 5: 9

Structures of BIR domains from human NAIP and cIAP2.

2010-04-28T13:26:59Z

The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray c...

Maria Dolores Herman, Martin Moche, Susanne Flodin, Martin Welin, Lionel Trésaugues, Ida Johansson, Martina Nilsson, Pär Nordlund, Tomas Nyman (2009) Acta Crystallogr Sect F Struct Biol Cryst Commun 65: Pt 11 1091-1096

The crystal structure of human cleavage and polyadenylation specific factor-5 reveals a dimeric Nudix protein with a conserved catalytic site.

2010-04-28T13:26:59Z

Lionel Trésaugues, Pål Stenmark, Herwig Schüler, Susanne Flodin, Martin Welin, Tomas Nyman, Martin Hammarström, Martin Moche, Susanne Gräslund, Pär Nordlund (2008) Proteins 73: 4 1047-1052

The crystal structure of the bifunctional deaminase/reductase RibD of the riboflavin biosynthetic pathway in Escherichia coli: implications for the reductive mechanism.

2010-04-28T13:23:00Z

We have determined the crystal structure of the bi-functional deaminase/reductase enzyme from Escherichia coli (EcRibD) that catalyzes two consecutive reactions during riboflavin biosynthesis. The polypeptide chain of EcRibD is folded into two domains where the 3D structure of the N-terminal domain (1-145) is similar to cytosine deaminase and the C-terminal domain (146-367) is similar to dihydrofo...

Pål Stenmark, Martin Moche, Daniel Gurmu, Pär Nordlund (2007) J Mol Biol 373: 1 48-64

A single mutation in the castor Delta9-18:0-desaturase changes reaction partitioning from desaturation to oxidase chemistry.

2010-04-28T13:25:08Z

Sequence analysis of the diiron cluster-containing soluble desaturases suggests they are unrelated to other diiron enzymes; however, structural alignment of the core four-helix bundle of desaturases to other diiron enzymes reveals a conserved iron binding motif with similar spacing in all enzymes of this structural class, implying a common evolutionary ancestry. Detailed structural comparison of t...

Jodie E Guy, Isabel A Abreu, Martin Moche, Ylva Lindqvist, Edward Whittle, John Shanklin (2006) Proc Natl Acad Sci U S A 103: 46 17220-17224

Azide and acetate complexes plus two iron-depleted crystal structures of the di-iron enzyme delta9 stearoyl-acyl carrier protein desaturase. Implications for oxygen activation and catalytic intermediates.

2010-04-28T13:26:59Z

Delta9 stearoyl-acyl carrier protein (ACP) desaturase is a mu-oxo-bridged di-iron enzyme, which belongs to the structural class I of large helix bundle proteins and that catalyzes the NADPH and O2-dependent formation of a cis-double bond in stearoyl-ACP. The crystal structures of complexes with azide and acetate, respectively, as well as the apoand single-iron forms of Delta9 stearoyl-ACP desatura...

Martin Moche, John Shanklin, Alokesh Ghoshal, Ylva Lindqvist (2003) J Biol Chem 278: 27 25072-25080

The crystal structure of beta-ketoacyl-acyl carrier protein synthase II from Synechocystis sp. at 1.54 A resolution and its relationship to other condensing enzymes.

2010-04-28T13:26:59Z

Condensing enzymes, catalyzing the formation of carbon-carbon bonds in several biosynthetic pathways, have lately been recognized as potential drug targets against cancer and tuberculosis, as crucial for combinatorial biosynthesis of antibiotics and related compounds, and as determinants of plant oil composition. beta-Ketoacyl-ACP synthases (KAS) are the condensing enzymes present in the fatty aci...

M Moche, K Dehesh, P Edwards, Y Lindqvist (2001) J Mol Biol 305: 3 491-503

Structure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase.

2010-04-28T13:26:59Z

In the biosynthesis of fatty acids, the beta-ketoacyl-acyl carrier protein (ACP) synthases catalyze chain elongation by the addition of two-carbon units derived from malonyl-ACP to an acyl group bound to either ACP or CoA. The enzyme is a possible drug target for treatment of certain cancers and for tuberculosis. The crystal structure of the complex of the enzyme from Escherichia coli, and the fun...

M Moche, G Schneider, P Edwards, K Dehesh, Y Lindqvist (1999) J Biol Chem 274: 10 6031-6034