© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
June 29, 2015
Very Important Paper: Critical Intermediates Reveal New Biosynthetic Events in the Enigmatic Colibactin Pathway
Zhong-Rui Li, Yongxin Li, Jennifer Y. H. Lai, Jianqiang Tang, Bin Wang, Liang Lu, Guoqiang Zhu, Xiyang Wu, Ying Xu, Pei-Yuan Qian*
It has been ten years since the discovery of the colibactin biosynthetic gene cluster, denoted the “pks island”. The pathogenicity and the underlying mechanisms of these pks+ strains are in the process of being elucidated. However, the precise chemical structure of colibactin remains elusive, which severely hampers attempts to acquire an in-depth understanding of this compound. Now, P.-Y. Qian (The Hong Kong University of Science and Technology) and co-workers isolated and identified a series of novel compounds as key (pre)colibactin intermediates. The 1H-pyrrolo[3,4-c]pyridine-3,6(2H,5H)-dione- and thiazole-containing intermediate and a dithiazole-containing intermediate discovered here set the stage for fully deciphering the biosynthetic pathway and understanding how colibactin causes DNA double-strand breaks in vivo.
Recently Published Articles
- Diversified Structural Basis of a Conserved Molecular Mechanism for pH-Dependent Dimerization in Spider Silk N-Terminal Domains
Martins Otikovs, Dr. Gefei Chen, Kerstin Nordling, Dr. Michael Landreh, Prof. Dr. Qing Meng, Dr. Hans Jörnvall, Dr. Nina Kronqvist, Dr. Anna Rising, Prof. Dr. Jan Johansson and Dr. Kristaps Jaudzems
Article first published online: 1 JUL 2015 | DOI: 10.1002/cbic.201500263
Spinning webs: Conversion of spider silk proteins from soluble dope to insoluble fibers involves pH-dependent dimerization of the N-terminal domain (NT). We have analyzed the pH dependence of the A. ventricosus minor ampullate spidroin NT and determined solution structures at pH 7.2 and 5.5, revealing that the dimerization is mediated by protonation of three glutamic acid residues.
- Direct Chemical Activation of a Rationally Engineered Signaling Enzyme
Cynthia M. Chio, Karen W. Cheng and Prof. Anthony C. Bishop
Article first published online: 30 JUN 2015 | DOI: 10.1002/cbic.201500245
Turn it on: Rational engineering of a loop at Shp2's interdomain interface yields a protein phosphatase that retains its mechanism of autoinhibitory regulation but can be target-specifically activated with a small molecule. This strategy for achieving direct chemical control over enzyme activity may be applicable to a range of signaling proteins, many of which are regulated through domain–domain interactions.
- Optimizing the Photocontrol of bZIP Coiled Coils with Azobenzene Crosslinkers: Role of the Crosslinking Site
Dr. Ahmed M. Ali, Dr. Matthew W. Forbes and Prof. G. Andrew Woolley
Article first published online: 30 JUN 2015 | DOI: 10.1002/cbic.201500191
Systematic testing of potential sites for cis/trans photoswitchable azobenzene-based crosslinkers leads to effective light-controlled inhibitors of CREB transcription factors. The largest degree of photocontrol is achieved when the crosslinker is in the zipper region between Cys residues in the heptad segment showing the highest intrinsic helical propensity.
- Tuning the pH Response of i-Motif DNA Oligonucleotides
Laurie Lannes, Saheli Halder, Dr. Yamuna Krishnan and Prof. Dr. Harald Schwalbe
Article first published online: 30 JUN 2015 | DOI: 10.1002/cbic.201500182
pH response shifting: The human telomeric DNA molecule I3 is able to adopt an i-motif conformation in response to pH change. Herein, we show that the pH response range of I3 can be shifted towards more basic pH values by introducing 5-methylcytidines and towards more acidic pH values by introducing 5-bromocytidines, which accelerated folding of the i-motif.
- Peptide Fragments of Odin-Sam1: Conformational Analysis and Interaction Studies with EphA2-Sam
Dr. Flavia A. Mercurio, Concetta Di Natale, Dr. Luciano Pirone, Dr. Pasqualina L. Scognamiglio, Dr. Daniela Marasco, Dr. Emilia M. Pedone, Dr. Michele Saviano and Dr. Marilisa Leone
Article first published online: 26 JUN 2015 | DOI: 10.1002/cbic.201500197
Taking a knife to the interface: Odin-Sam1 was dissected into three different fragments encompassing its mid-loop interaction interface for EphA2-Sam along with the C-terminal helix α5. The peptides were disordered in H2O but highly helical in the presence of trifluoroethanol. The binding of the isolated protein regions towards EphA2-Sam was poor.