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1.  Short peptides self-assemble to produce catalytic amyloids 
Nature chemistry  2014;6(4):303-309.
Enzymes fold into unique three-dimensional structures, which underlie their remarkable catalytic properties. The requirement to adopt a stable, folded conformation is likely to contribute to their relatively large size (> 10,000 Dalton). However, much shorter peptides can achieve well-defined conformations through the formation of amyloid fibrils. To test whether short amyloid-forming peptides might in fact be capable of enzyme-like catalysis, we designed a series of 7-residue peptides that act as Zn2+-dependent esterases. Zn2+ helps stabilize the fibril formation, while also acting as a cofactor to catalyze acyl ester hydrolysis. These results indicate that prion-like fibrils are able to not only catalyze their own formation – they also can catalyze chemical reactions. Thus, they might have served as intermediates in the evolution of modern-day enzymes. These results also have implications for the design of self-assembling nanostructured catalysts including ones containing a variety of biological and nonbiological metal ions.
doi:10.1038/nchem.1894
PMCID: PMC3996680  PMID: 24651196
2.  A Single Mutation in a Regulatory Protein Produces Evolvable Allosterically Regulated Catalyst of Unnatural Reaction 
Angewandte Chemie (International ed. in English)  2013;52(24):10.1002/anie.201302339.
It only takes one mutation: a strategically placed single mutation in a non-enzymatic protein scaffold produced AlleyCat, a small, allosterically regulated catalyst of Kemp elimination. In only 7 rounds of directed evolution enzymatic efficiency of the original 74 amino acid residue catalyst was improved more than 220-fold to achieve kcat value higher than that of catalytic antibodies for the same reaction, still preserving allosteric regulation.
doi:10.1002/anie.201302339
PMCID: PMC3817844  PMID: 23630096
Metalloproteins; Catalysts; Enzyme catalysis
3.  Painting Proteins Blue: β-(1-Azulenyl)-L-Alanine as a Probe for Studying Protein-Protein Interactions 
Chemical communications (Cambridge, England)  2013;49(5):10.1039/c2cc37550h.
We demonstrated that β-(1-Azulenyl)-L-Alanine, a fluorescent pseudoisosteric analog of tryptophan, exhibits weak environmental dependence and thus allows for using weak intrinsic quenchers, such as methionines, to monitor protein-protein interactions while not perturbing them.
doi:10.1039/c2cc37550h
PMCID: PMC3547328  PMID: 23207368
4.  Isolated Toll-like Receptor Transmembrane Domains Are Capable of Oligomerization 
PLoS ONE  2012;7(11):e48875.
Toll-like receptors (TLRs) act as the first line of defense against bacterial and viral pathogens by initiating critical defense signals upon dimer activation. The contribution of the transmembrane domain in the dimerization and signaling process has heretofore been overlooked in favor of the extracellular and intracellular domains. As mounting evidence suggests that the transmembrane domain is a critical region in several protein families, we hypothesized that this was also the case for Toll-like receptors. Using a combined biochemical and biophysical approach, we investigated the ability of isolated Toll-like receptor transmembrane domains to interact independently of extracellular domain dimerization. Our results showed that the transmembrane domains had a preference for the native dimer partners in bacterial membranes for the entire receptor family. All TLR transmembrane domains showed strong homotypic interaction potential. The TLR2 transmembrane domain demonstrated strong heterotypic interactions in bacterial membranes with its known interaction partners, TLR1 and TLR6, as well as with a proposed interaction partner, TLR10, but not with TLR4, TLR5, or unrelated transmembrane receptors providing evidence for the specificity of TLR2 transmembrane domain interactions. Peptides for the transmembrane domains of TLR1, TLR2, and TLR6 were synthesized to further study this subfamily of receptors. These peptides validated the heterotypic interactions seen in bacterial membranes and demonstrated that the TLR2 transmembrane domain had moderately strong interactions with both TLR1 and TLR6. Combined, these results suggest a role for the transmembrane domain in Toll-like receptor oligomerization and as such, may be a novel target for further investigation of new therapeutic treatments of Toll-like receptor mediated diseases.
doi:10.1371/journal.pone.0048875
PMCID: PMC3498381  PMID: 23155421
5.  Tris{2-[(2,6-dimethyl­phen­yl)amino]­eth­yl}amine 
The title compound, C30H42N4, is an aryl­ated tris­(amino­eth­yl)amine derivative which was obtained by reducing the corresponding tris-amide with AlH3. The asymmetric unit consists of one third of a C 3v-symmetric mol­ecule with the tertiary N atom lying on a crystallographic threefold axis.
doi:10.1107/S1600536811049397
PMCID: PMC3239057  PMID: 22199905
6.  N′-(2-Hy­droxy­benzyl­idene)-2-(hy­droxy­imino)­propano­hydrazide 
The mol­ecule of the title compound, C10H11N3O3, adopts an all-trans conformation and is approxomately planar, the largest deviation from the least-squares plane through all non-H atoms being 0.261 (1) Å. An intra­molecular O—H⋯N hydrogen bond occurs. In the crystal, the mol­ecules are packed into layers lying parallel to the ab plane by π-stacking inter­actions between the benzene ring of one molecule and the C—N bond of the oxime group of another molecule; the shortest inter­molecular C⋯C separation within the layer is 3.412 (1) Å. The layers are connected by O—H⋯O and N—H⋯O hydrogen bonds.
doi:10.1107/S1600536811045818
PMCID: PMC3238939  PMID: 22199788
7.  Bis(μ2-η2:η2-2,4,6-trimethyl­benzonitrile)­bis­[(N-isopropyl-3,5-dimethyl­anilido)molybdenum(III)](Mo—Mo) 
The title compound, [Mo2(C11H16N)4(C10H11N)2], is a dinuclear molybdenum complex with a formal metal–metal bond [Mo⋯Mo separation = 2.5946 (8) Å], four anilide-type ligands and two bridging mesityl nitrile groups. There are two inversion symmetric mol­ecules in the unit cell (an inversion center is localized at the mid-point of the Mo—Mo bond), each with approximate non-crystallographic C 2h symmetry. The mol­ecules contain disordered isopropyl and 3,5-C6H3Me2 groups on different anilido ligands; the major component having an occupancy of 0.683 (7). The complex was obtained in low yield as the product from the reaction between the bridging pyrazine adduct of molybdenum tris­-anilide ([μ2-(C4H4N2){Mo(C11H16N)3}2]) and mesityl nitrile with a loss of one anilido ligand.
doi:10.1107/S1600536811044680
PMCID: PMC3238583  PMID: 22199474
8.  catena-Poly[[[aqua­copper(II)]bis­[μ-bis(3,5-dimethyl-1H-pyrazol-4-yl) selenide]] bis­(tetra­fluorido­borate) bis­(triphenyl­phosphine oxide) monohydrate] 
The title compound, {[Cu(C10H14N4Se)2(H2O)](BF4)2·2C18H15PO·H2O}n, has a polymeric structure where each CuII ion adopts a square-pyramidal coordination constituted by four N atoms of pyrazole moieties in the equatorial plane and an axial O atom of a water mol­ecule. A pair of bis­(3,5-dimethyl-1H-pyrazol-4-yl) selenide ligands bridges the CuII centres into a chain extending along the c axis. The water mol­ecules, anions and triphenyl­phosphine oxide mol­ecules are involved in inter­molecular hydrogen bonding, which links the chains into a three-dimensional network.
doi:10.1107/S1600536810012997
PMCID: PMC2979014  PMID: 21579021
9.  catena-Poly[[[aqua­copper(II)]-bis­[μ-bis­(3,5-dimethyl-1H-pyrazol-4-yl) selenide-κ2 N 2:N 2′]] dichloride monohydrate] 
In the title compound, {[Cu(C10H14N4Se)2(H2O)]Cl2·H2O}n, the CuII ion, lying on a twofold rotation axis, has a square-pyramidal geometry constituted by four N atoms of pyrazolyl groups in the basal plane and an apical O atom of a water mol­ecule. A pair of bis­(3,5-dimethyl-1H-pyrazol-4-yl) selenide ligands bridge the Cu centers into a polymeric double-chain extending along [001]. The chloride anions are involved in inter­molecular N—H⋯Cl and O—H⋯Cl hydrogen bonds, which link the chains into a three-dimensional network.
doi:10.1107/S1600536810007403
PMCID: PMC2983851  PMID: 21580477
10.  Bis{2-hydroxy­imino-N′-[1-(2-pyrid­yl)ethyl­idene]propanohydrazidato}zinc(II) dihydrate 
The title compound, [Zn(C10H11N4O2)2]·2H2O, was prepared by the reaction between Zn(CH3COO)2·2H2O and 2-hydroxy­imino-N′-[1-(2-pyrid­yl)ethyl­idene]propano­hydrazide (Hpop). The central ZnII atom has a distorted tetra­gonal-bipyramidal coordination geometry formed by two amide O atoms and four N atoms of two azomethine and two pyridine groups. In the crystal, complex mol­ecules form layers parallel to the crystallographic b direction. The layers are connected by O—H⋯N and O—H⋯O hydrogen bonds involving the solvent water mol­ecules.
doi:10.1107/S1600536810003351
PMCID: PMC2979945  PMID: 21579695
11.  (2E)-2-Hydroxy­imino-N′-[(E)-2-pyridyl­methyl­ene]propanohydrazide 
In the title compound, C9H10N4O2, the pyridine ring is twisted by 16.5 (1)° from the mean plane defined by the remaining non-H atoms. An intra­molecular N—H⋯N inter­action is present. In the crystal, inter­molecular O—H⋯N and N—H⋯O hydrogen bonds link mol­ecules into layers parallel to the bc plane. The crystal packing exhibits π–π inter­actions indicated by the short distance of 3.649 (1) Å between the centroids of the pyridine rings of neighbouring mol­ecules.
doi:10.1107/S1600536809034400
PMCID: PMC2970200  PMID: 21577872
12.  2-Hydroxy­imino-N′-[1-(2-pyrid­yl)ethyl­idene]propanohydrazide 
The title compound, C10H12N4O2, features an intra­molecular N—H⋯N hydrogen bond formed between the imine NH and oxime N atoms. The oxime group and the amide C=O bond are anti to each other. In the crystal, mol­ecules are connected by O—H⋯O hydrogen bonds into supra­molecular zigzag chains along the c axis.
doi:10.1107/S1600536809033352
PMCID: PMC2969988  PMID: 21577640
13.  Dichlorido{2-hydroxy­imino-N′-[1-(2-pyrid­yl)ethyl­idene]propanohydrazide-κ3 N,N′,O}zinc(II) hemihydrate 
The title compound, [ZnCl2(C10H12N4O2)]·0.5H2O, was readily prepared by the reaction between ZnCl2 and 2-hydroxy­imino-N′-[1-(2-pyrid­yl)ethyl­idene]propanohydrazide. The Zn atom has a distorted trigonal–bipyramidal geometry with two Cl atoms and one azomethine N atom in the equatorial plane and one pyridine N atom and one amide O atom in the axial positions. In the crystal structure, complex mol­ecules are connected in pairs by N—H⋯Cl hydrogen bonds, formed between the amide NH of one mol­ecule and the Cl atom of a neighboring one. Mol­ecular pairs are connected by hydrogen bonds involving the uncoordinated water mol­ecule, which lies on a twofold axis.
doi:10.1107/S160053680706535X
PMCID: PMC2960173  PMID: 21201313

Results 1-13 (13)