@article {2303,
	title = {The crystal structure of MexR from Pseudomonas aeruginosa in complex with its antirepressor ArmR},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {105},
	number = {39},
	year = {2008},
	note = {ISI Document Delivery No.: 386WWTimes Cited: 15Cited Reference Count: 41Wilke, Mark S. Heller, Markus Creagh, A. Louise Haynes, Charles A. McIntosh, Lawrence P. Poole, Keith Strynadka, Natalie C. J.},
	month = {Sep},
	pages = {14832-14837},
	type = {Article},
	abstract = {The intrinsic antimicrobial resistance of the opportunistic human pathogen Pseudomonas aeruginosa is compounded in mutant strains that overexpress multidrug efflux pumps such as the prominent drug-proton antiporter, MexAB-OprM. The primary regulator of the mexAB-oprM operon is the MarR family repressor, MexR. An additional repressor, NalC, also regulates mexAB-oprM by controlling expression of ArmR, an antirepressor peptide that is hypothesized to prevent the binding of MexR to its cognate DNA operator via an allosteric protein-peptide interaction. To better understand how ArmR modulates MexR, we determined the MexR-binding region of ArmR as its C-terminal 25 residues and solved the crystal structure of MexR in a 2: 1 complex with this ArmR fragment at 1.8 angstrom resolution. This structure reveals that the C-terminal residues of ArmR form a kinked alpha-helix, which occupies a pseudo-symmetrical and largely hydrophobic binding cavity located at the centre of the MexR dimer. Although the ArmR-binding cavity partially overlaps with the small molecule effector-binding sites of other MarR family members, it possesses a larger and more complex binding surface to accommodate the greater size and specific physicochemical properties of a peptide effector. Comparison with the structure of apo-MexR reveals that ArmR stabilizes a dramatic conformational change that is incompatible with DNA-binding. Thus, this work defines the structural mechanism by which ArmR allosterically derepresses MexR-controlled gene expression in P. aeruginosa and reveals important insights into the regulation of multidrug resistance.},
	keywords = {DEINOCOCCUS-RADIODURANS, DNA-BINDING, EXPRESSION, GENE, gene regulation, MarR, MARR FAMILY, MECHANISM, mexAB-oprM, MULTIDRUG EFFLUX OPERON, OPRM, PA3719, protein peptide, REPRESSOR, TRANSCRIPTIONAL REGULATOR HUCR},
	isbn = {0027-8424},
	url = {<Go to ISI>://000261914300004},
	author = {Wilke, M. S. and Heller, M. and Creagh, A. L. and Haynes, C. A. and McIntosh, L. P. and Poole, K. and Strynadka, N. C. J.}
}
@article {1473,
	title = {Beads-on-a-string, characterization of Ets-1 sumoylated within its flexible N-terminal sequence},
	journal = {Journal of Biological Chemistry},
	volume = {281},
	number = {7},
	year = {2006},
	note = {ISI Document Delivery No.: 011NNTimes Cited: 11Cited Reference Count: 62},
	month = {Feb},
	pages = {4164-4172},
	type = {Article},
	abstract = {Sumoylation regulates the activities of several members of the ETS transcription factor family. To provide a molecular framework for understanding this regulation, we have characterized the conjugation of Ets-1 with SUMO-1. Ets-1 is modified in vivo predominantly at a consensus sumoylation motif containing Lys-15. This lysine is located within the unstructured N-terminal segment of Ets-1 preceding its PNT domain. Using NMR spectroscopy, we demonstrate that the Ets-1 sumoylation motif associates with the substrate binding site on the SUMO-conjugating enzyme UBC9 (K-d similar to 400 mu M) and that the PNT domain is not involved in this interaction. Ets-1 with Lys-15 mutated to an arginine still binds UBC9 with an affinity similar to the wild type protein, but is no longer sumoylated. NMR chemical shift and relaxation measurements reveal that the covalent attachment of mature SUMO-1, via its flexible C-terminal Gly-97, to Lys-15 of Ets-1 does not perturb the structure or dynamic properties of either protein. Therefore sumoylated Ets-1 behaves as "beads-on-a-string" with the two proteins tethered by flexible polypeptide segments containing the isopeptide linkage. Accordingly, SUMO-1 may mediate interactions of Ets-1 with signaling or transcriptional regulatory macromolecules by acting as a structurally independent docking module, rather than through the induction of a conformational change in either protein upon their covalent linkage. We also hypothesize that the flexibility of the linking polypeptide sequence may be a general feature contributing to the recognition of SUMO-modified proteins by their downstream effectors.},
	keywords = {BACKBONE DYNAMICS, CRYSTAL-STRUCTURE, DNA-BINDING, MODIFICATION, NMR-SPECTROSCOPY, NUCLEAR-BODIES, POINTED DOMAIN, SUMO, TRANSCRIPTIONAL REPRESSION, TUMOR-SUPPRESSOR, UBIQUITIN-CONJUGATING ENZYME},
	isbn = {0021-9258},
	url = {<Go to ISI>://000235275300048},
	author = {Macauley, M. S. and Errington, W. J. and Scharpf, M. and Mackereth, C. D. and Blaszczak, A. G. and Graves, B. J. and McIntosh, L. P.}
}
@article {4406,
	title = {Assigning the NMR spectra of aromatic amino acids in proteins: analysis of two Ets pointed domains},
	journal = {Biochemistry and Cell Biology-Biochimie Et Biologie Cellulaire},
	volume = {76},
	number = {2-3},
	year = {1998},
	note = {ISI Document Delivery No.: 157QRTimes Cited: 11Cited Reference Count: 34},
	pages = {379-390},
	type = {Article},
	abstract = {The measurement of interproton nuclear Overhauser enhancements (NOEs) and dihedral angle restraints of aromatic amino acids is a critical step towards determining the structure of a protein. The complete assignment of the resonances from aromatic rings and the subsequent resolution and identification of their associated NOEs, however, can be a difficult task. Shown here is a strategy for assigning the H-1,C-13, and N-15 signals from the aromatic side chains of histidine, tryptophan, tyrosine, and phenylalanine using a suite of homo- and hetero-nuclear scalar and NOE correlation experiments, as well as selective deuterium isotope labelling. In addition, a comparison of NOE information obtained from homonuclear NOE spectroscopy (NOESY) and C-13-edited NOESY - heteronuclear single quantum correlation experiments indicates that high-resolution homonuclear two-dimensional NOESY spectra of selectively deuterated proteins are invaluable for obtaining distance restraints to the aromatic residues.},
	keywords = {ACTIVE-SITE, ANGLE, aromatic residue, BACKBONE H-1, C-13-LABELED PROTEINS, CHEMICAL-SHIFTS, dihedral, DNA-BINDING, HETERONUCLEAR NMR, HISTIDINE-RESIDUES, MAGNETIC-RESONANCE SPECTROSCOPY, NMR assignment, NOE, pH titration, PHENYLALANINE RESIDUES, TRANSCRIPTION FACTOR},
	isbn = {0829-8211},
	url = {<Go to ISI>://000078073600026},
	author = {Slupsky, C. M. and Gentile, L. N. and McIntosh, L. P.}
}
