@article {Daniel-Ivad2024-fb,
	title = {An imine reductase that captures reactive intermediates in the biosynthesis of the indolocarbazole reductasporine},
	journal = {J. Biol. Chem.},
	volume = {300},
	number = {2},
	year = {2024},
	pages = {105642},
	publisher = {Elsevier BV},
	abstract = {Imine reductases (IREDs) and reductive aminases have been used in the synthesis of chiral amine products for drug manufacturing; however, little is known about their biological contexts. Here we employ structural studies and site-directed mutagenesis to interrogate the mechanism of the IRED RedE from the biosynthetic pathway to the indolocarbazole natural product reductasporine. Cocrystal structures with the substrate-mimic arcyriaflavin A reveal an extended active site cleft capable of binding two indolocarbazole molecules. Site-directed mutagenesis of a conserved aspartate in the primary binding site reveals a new role for this residue in anchoring the substrate above the NADPH cofactor. Variants targeting the secondary binding site greatly reduce catalytic efficiency, while accumulating oxidized side-products. As indolocarbazole biosynthetic intermediates are susceptible to spontaneous oxidation, we propose the secondary site acts to protect against autooxidation, and the primary site drives catalysis through precise substrate orientation and desolvation effects. The structure of RedE with its extended active site can be the starting point as a new scaffold for engineering IREDs and reductive aminases to intercept large substrates relevant to industrial applications.},
	keywords = {biosynthesis, enzyme catalysis, enzyme structure, imine reductase, indolocarbazole, SITE-DIRECTED MUTAGENESIS, X-RAY CRYSTALLOGRAPHY},
	author = {Daniel-Ivad, Phillip and Ryan, Katherine S}
}
@article {1064,
	title = {Molecular mechanics-assisted crystal engineering of solid state photoreactions: application to the Yang photocyclization of alpha-1-norbornylacetophenone derivatives},
	journal = {Tetrahedron Letters},
	volume = {46},
	number = {7},
	year = {2005},
	note = {ISI Document Delivery No.: 895FRTimes Cited: 3Cited Reference Count: 11},
	month = {Feb},
	pages = {1141-1144},
	type = {Article},
	abstract = {Based on molecular mechanics, Yang photocyclization of alpha-1-norbornylacetophenone derivatives in the crystalline state was engineered through methylation adjacent to the carbonyl group, thus changing the conformation in the crystal and leading to enhanced diastereo- and enantioselectivity. (C) 2004 Elsevier Ltd. All rights reserved.},
	keywords = {ASYMMETRIC INDUCTION, crystal engineering, GEOMETRIC REQUIREMENTS, II REACTION, ionic chiral auxiliaries, REACTIVITY, solid state photochemistry, X-RAY CRYSTALLOGRAPHY, Yang photocyclization},
	isbn = {0040-4039},
	url = {<Go to ISI>://000226846800021},
	author = {Botoshansky, M. and Braga, D. and Kaftory, M. and Maini, L. and Patrick, B. O. and Scheffer, J. R. and Wang, K. Y.}
}
@article {4842,
	title = {Hydrogen bonding and catalysis: A novel explanation for how a single amino acid substitution can change the pH optimum of a glycosidase},
	journal = {Journal of Molecular Biology},
	volume = {299},
	number = {1},
	year = {2000},
	note = {ISI Document Delivery No.: 318NCTimes Cited: 96Cited Reference Count: 58},
	month = {May},
	pages = {255-279},
	type = {Article},
	abstract = {The pH optima of family 11 xylanases are well correlated with the nature of the residue adjacent to the acid/base catalyst. In xylanases that function optimally under acidic conditions, this residue is aspartic acid, whereas it is asparagine in those that function under more alkaline conditions. Previous studies of wild-type (WT) Bacillus circulans xylanase (BCX), with an asparagine residue at position 35, demonstrated that its pH-dependent activity follows the ionization states of the nucleophile Glu78 (pK(a) 4.6) and the acid/base catalyst Glu172 (pK(a) 6.7). As predicted from sequence comparisons, substitution of this asparagine residue with an aspartic acid residue (N35D BCX) shifts its pH optimum from 5.7 to 4.6, with an similar to 20 \% increase in activity. The bell-shaped pH-activity profile of this mutant enzyme follows apparent pK(a) values of 3.5 and 5.8. Based on C-13-NMR titrations, the predominant pK(a) values of its active-site carboxyl groups are 3.7 (Asp35), 5.7 (Glu78) and 8.4 (Glu172). Thus, in contrast to the WT enzyme, the pH-activity profile of N35D BCX appears to be set by Asp35 and Glu78. Mutational, kinetic, and structural studies of N35D BCX, both in its native and covalently modified 2-fluoro-xylobiosyl glycosyl-enzyme intermediate states, reveal that the xylanase still follows a double-displacement mechanism with Glu78 serving as the nucleophile. We therefore propose that Asp35 and Glu172 function together as the general acid/base catalyst, and that N35D BCX exhibits a "reverse protonation" mechanism in which it is catalytically active when Asp35, with the lower pK(a), is protonated, while Glu78, with the higher pK(a), is deprotonated. This implies that the mutant enzyme must have an inherent catalytic efficiency at least 100-fold higher than that of the parental WT, because only similar to 1\% of its population is in the correct ionization state for catalysis at its pH optimum. The increased efficiency of N35D BCX, and by inference all "acidic" family 11 xylanases, is attributed to the formation of a short (2.7 Angstrom) hydrogen bond between Asp35 and Glu172, observed in the crystal structure of the glycosyl-enzyme intermediate of this enzyme, that will substantially stabilize the transition state for glycosyl transfer. Such a mechanism may be much more commonly employed than is generally realized, necessitating careful analysis of the pH-dependence of enzymatic catalysis. (C) 2000 Academic Press.},
	keywords = {3-DIMENSIONAL STRUCTURE, 4-BETA-XYLANASES, ACTIVE-SITE, BACILLUS-CIRCULANS XYLANASE, CYCLODEXTRIN GLYCOSYLTRANSFERASE, electrostatics, ENDO-1, GLYCOSYL-ENZYME INTERMEDIATE, ISOTOPE, MOLECULAR-WEIGHT, NMR, NUCLEAR-MAGNETIC-RESONANCE, nucleophile, PANCREATIC ALPHA-AMYLASE, pH-dependent enzyme mechanism, SHIFT, TRICHODERMA-REESEI, X-RAY CRYSTALLOGRAPHY, X-ray structure},
	isbn = {0022-2836},
	url = {<Go to ISI>://000087289400019},
	author = {Joshi, M. D. and Sidhu, G. and Pot, I. and Brayer, G. D. and Withers, S. G. and McIntosh, L. P.}
}
@article {4507,
	title = {In the footsteps of Pasteur: Asymmetric induction in the solid-state photochemistry of ammonium carboxylate salts},
	journal = {Journal of the American Chemical Society},
	volume = {121},
	number = {12},
	year = {1999},
	note = {ISI Document Delivery No.: 182QRTimes Cited: 23Cited Reference Count: 10},
	month = {Mar},
	pages = {2919-2920},
	type = {Article},
	keywords = {X-RAY CRYSTALLOGRAPHY},
	isbn = {0002-7863},
	url = {<Go to ISI>://000079510100032},
	author = {Cheung, E. and Netherton, M. R. and Scheffer, J. R. and Trotter, J.}
}
@article {4507,
	title = {In the footsteps of Pasteur: Asymmetric induction in the solid-state photochemistry of ammonium carboxylate salts},
	journal = {Journal of the American Chemical Society},
	volume = {121},
	number = {12},
	year = {1999},
	note = {ISI Document Delivery No.: 182QRTimes Cited: 23Cited Reference Count: 10},
	month = {Mar},
	pages = {2919-2920},
	type = {Article},
	keywords = {X-RAY CRYSTALLOGRAPHY},
	isbn = {0002-7863},
	url = {<Go to ISI>://000079510100032},
	author = {Cheung, E. and Netherton, M. R. and Scheffer, J. R. and Trotter, J.}
}
@article {3625,
	title = {Synthesis of meso-phenyl-4,6-dipyrrins, preparation of their Cu(II), Ni(II), and Zn(II) chelates, and structural characterization of bis[meso-phenyl-4,6-dipyrrinato]Ni(II)},
	journal = {Canadian Journal of Chemistry-Revue Canadienne De Chimie},
	volume = {74},
	number = {11},
	year = {1996},
	note = {ISI Document Delivery No.: WC124Times Cited: 73Cited Reference Count: 58},
	month = {Nov},
	pages = {2182-2193},
	type = {Article},
	abstract = {{meso-Phenyldipyrromethanes can be oxidized by 2,6-dicyano-3,5-dichloro-para-benzoquinone (DDQ) to the corresponding meso-phenyldipyrrins. As expected, these novel, stable bipyrrolic pigments readily form metal chelates with copper(II), nickel(II), and zinc(II). Their W-VIS spectra are compared with a series of blown alkyl-substituted dipyrrin chelates and, based oil the W-VIS spectral analysis, the dihedral angle between the two ligands iri the bis[meso-phenyldipyrrinato]Ni(II) complex was calculated to be 42 degrees. The molecular structure of this complex was determined by X-ray crystallography, essentially confirming the calculation. Crystals of C30H22N4Ni are orthorhombic},
	keywords = {CRYSTAL-STRUCTURE, DIPYRROMETHENES, LIGANDS, meso-phenyldipyrrinato transition metal chelates, meso-phenyldipyrrins, meso-phenyldipyrromethanes, MOLECULAR, PYRROLE PIGMENTS, STEREOCHEMISTRY, TRANSITION-METAL COMPLEXES, X-RAY CRYSTALLOGRAPHY},
	isbn = {0008-4042},
	url = {<Go to ISI>://A1996WC12400032},
	author = {Bruckner, C. and Karunaratne, V. and Rettig, S. J. and Dolphin, D.}
}
