Boyd AE

General

Full name : Boyd Aileen E

First name : Aileen E

Mail : Dept. of Pharmacology, UCSD 9500 Gilman Dr. La Jolla, CA 92093-0636

Zip Code :

City :

Country : USA

Email : aboyd@ucsd.edu

Phone : 619-534-2890

Fax : 619-534-8248

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References (9)

Title : The genome of Eucalyptus grandis - Myburg_2014_Nature_510_356
Author(s) : Myburg AA , Grattapaglia D , Tuskan GA , Hellsten U , Hayes RD , Grimwood J , Jenkins J , Lindquist E , Tice H , Bauer D , Goodstein DM , Dubchak I , Poliakov A , Mizrachi E , Kullan AR , Hussey SG , Pinard D , van der Merwe K , Singh P , van Jaarsveld I , Silva-Junior OB , Togawa RC , Pappas MR , Faria DA , Sansaloni CP , Petroli CD , Yang X , Ranjan P , Tschaplinski TJ , Ye CY , Li T , Sterck L , Vanneste K , Murat F , Soler M , Clemente HS , Saidi N , Cassan-Wang H , Dunand C , Hefer CA , Bornberg-Bauer E , Kersting AR , Vining K , Amarasinghe V , Ranik M , Naithani S , Elser J , Boyd AE , Liston A , Spatafora JW , Dharmwardhana P , Raja R , Sullivan C , Romanel E , Alves-Ferreira M , Kulheim C , Foley W , Carocha V , Paiva J , Kudrna D , Brommonschenkel SH , Pasquali G , Byrne M , Rigault P , Tibbits J , Spokevicius A , Jones RC , Steane DA , Vaillancourt RE , Potts BM , Joubert F , Barry K , Pappas GJ , Strauss SH , Jaiswal P , Grima-Pettenati J , Salse J , Van de Peer Y , Rokhsar DS , Schmutz J
Ref : Nature , 510 :356 , 2014
Abstract : Eucalypts are the world's most widely planted hardwood trees. Their outstanding diversity, adaptability and growth have made them a global renewable resource of fibre and energy. We sequenced and assembled >94% of the 640-megabase genome of Eucalyptus grandis. Of 36,376 predicted protein-coding genes, 34% occur in tandem duplications, the largest proportion thus far in plant genomes. Eucalyptus also shows the highest diversity of genes for specialized metabolites such as terpenes that act as chemical defence and provide unique pharmaceutical oils. Genome sequencing of the E. grandis sister species E. globulus and a set of inbred E. grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression. The E. grandis genome is the first reference for the eudicot order Myrtales and is placed here sister to the eurosids. This resource expands our understanding of the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology.
ESTHER : Myburg_2014_Nature_510_356
PubMedSearch : Myburg_2014_Nature_510_356
PubMedID: 24919147
Gene_locus related to this paper: eucgr-a0a059d0n8 , eucgr-a0a059cm68 , eucgr-a0a059d783 , eucgr-a0a059af93 , eucgr-a0a059awi0 , eucgr-a0a059awt4 , eucgr-a0a059ar83 , eucgr-a0a059ayw5 , eucgr-a0a059az75 , eucgr-a0a059azj1 , eucgr-a0a059azq5 , eucgr-a0a059bkm2 , eucgr-a0a059bl38 , eucgr-a0a059a7m2 , eucgr-a0a059a6p6 , eucgr-a0a059a6p1 , eucgr-a0a059a5e9 , eucgr-a0a059cpq4 , eucgr-a0a059b8v5

Title : Nanosecond dynamics of acetylcholinesterase near the active center gorge - Boyd_2004_J.Biol.Chem_279_26612
Author(s) : Boyd AE , Dunlop CS , Wong L , Radic Z , Taylor P , Johnson DA
Ref : Journal of Biological Chemistry , 279 :26612 , 2004
Abstract : To delineate the role of peptide backbone flexibility and rapid molecular motion in acetylcholinesterase catalysis and inhibitor association, we investigated the decay of fluorescence anisotropy at three sites of fluorescein conjugation to cysteine-substitution mutants of the enzyme. One cysteine was placed in a loop at the peripheral site near the rim of the active center gorge (H287C); a second was in a helical region outside of the active center gorge (T249C); a third was at the tip of a small, flexible omega loop well separated from the gorge (A262C). Mutation and fluorophore conjugation did not appreciably alter catalytic or inhibitor binding parameters of the enzyme. The results show that each site examined was associated with a high degree of segmental motion; however, the A262C and H287C sites were significantly more flexible than the T249C site. Association of the active center inhibitor, tacrine, and the peripheral site peptide inhibitor, fasciculin, had no effect on the anisotropy decay of fluorophores at positions 249 and 262. Fasciculin, but not tacrine, on the other hand, dramatically altered the decay profile of the fluorophore at the 287 position, in a manner consistent with fasciculin reducing the segmental motion of the peptide chain in this local region. The results suggest that the motions of residues near the active center gorge and across from the Cys(69)-Cys(96) omega loop are uncoupled and that ligand binding at the active center or the peripheral site does not influence acetylcholinesterase conformational dynamics globally, but induces primarily domain localized decreases in flexibility proximal to the bound ligand.
ESTHER : Boyd_2004_J.Biol.Chem_279_26612
PubMedSearch : Boyd_2004_J.Biol.Chem_279_26612
PubMedID: 15078872

Title : Poster (13) Conformational dynamics accompanying substrate and inhibitor binding to acetylcholinesterase. -
Author(s) : Taylor P , Shi J , Johnson DA , Boyd AE , Radic Z
Ref : In: Cholinesterases in the Second Millennium: Biomolecular and Pathological Aspects , (Inestrosa NC, Campos EO) P. Universidad Catolica de Chile-FONDAP Biomedicina :327 , 2004
PubMedID:

Title : Spectroscopic approaches to the study of acetylcholinesterase structure and function -
Author(s) : Taylor P , Shi J , Radic Z , Boyd AE , Johnson DA
Ref : In: Cholinesterases in the Second Millennium: Biomolecular and Pathological Aspects , (Inestrosa NC, Campos EO) P. Universidad Catolica de Chile-FONDAP Biomedicina :177 , 2004
PubMedID:

Title : Ligand-induced conformational changes in the omega loop of acetylcholinesterase revealed by fluorescence spectroscopy. -
Author(s) : Shi J , Radic Z , Boyd AE , Johnson DA , Taylor P
Ref : Cholinergic Mechanisms, CRC Press :695 , 2004
PubMedID:

Title : Reversibly bound and covalently attached ligands induce conformational changes in the Omega loop, Cys 69-Cys 96, of mouse acetylcholinesterase - Shi_2001_J.Biol.Chem_276_42196
Author(s) : Shi J , Boyd AE , Radic Z , Taylor P
Ref : Journal of Biological Chemistry , 276 :42196 , 2001
Abstract : We have used a combination of cysteine substitution mutagenesis and site-specific labeling to characterize the structural dynamics of mouse acetylcholinesterase (mAChE). Six cysteine-substituted sites of mAChE (Leu(76), Glu(81), Glu(84), Tyr(124), Ala(262), and His(287)) were labeled with the environmentally sensitive fluorophore, acrylodan, and the kinetics of substrate hydrolysis and inhibitor association were examined along with spectroscopic characteristics of the acrylodan-conjugated, cysteine-substituted enzymes. Residue 262, being well removed from the active center, appears unaffected by inhibitor binding. Following the binding of ligand, hypsochromic shifts in emission of acrylodan at residues 124 and 287, located near the perimeter of the gorge, reflect the exclusion of solvent and a hydrophobic environment created by the associated ligand. By contrast, the bathochromic shifts upon inhibitor binding seen for acrylodan conjugated to three omega loop (Omega loop) residues 76, 81, and 84 reveal that the acrylodan side chains at these positions are displaced from a hydrophobic environment and become exposed to solvent. The magnitude of fluorescence emission shift is largest at position 84 and smallest at position 76, indicating that a concerted movement of residues on the Omega loop accompanies gorge closure upon ligand binding. Acrylodan modification of substituted cysteine at position 84 reduces ligand binding and steady-state kinetic parameters between 1 and 2 orders of magnitude, but a similar substitution at position 81 only minimally alters the kinetics. Thus, combined kinetic and spectroscopic analyses provide strong evidence that conformational changes of the Omega loop accompany ligand binding.
ESTHER : Shi_2001_J.Biol.Chem_276_42196
PubMedSearch : Shi_2001_J.Biol.Chem_276_42196
PubMedID: 11517229

Title : Synthesis of fluorescent probes directed to the active site gorge of acetylcholinesterase - Saltmarsh_2000_Bioorg.Med.Chem.Lett_10_1523
Author(s) : Saltmarsh JR , Boyd AE , Rodriguez OP , Radic Z , Taylor P , Thompson CM
Ref : Bioorganic & Medicinal Chemistry Lett , 10 :1523 , 2000
Abstract : Six organophosphorus compounds linked to fluorophore groups were prepared in an effort to selectively modify the active site of acetylcholinesterase and deliver probes to the gorge region. Two compounds that vary by the length of a methylene (CH2) group, pyrene-SO2NH(CH2)nNHC(O)CH2CH2P(O)(OEt)(F) (where n = 2 or 3) were found to be potent, irreversible inhibitors of recombinant mouse AChE (Ki approximately 10(5) M(-1) min(-1)). Size exclusion chromatography afforded a fluorescently-labeled cholinesterase conjugate.
ESTHER : Saltmarsh_2000_Bioorg.Med.Chem.Lett_10_1523
PubMedSearch : Saltmarsh_2000_Bioorg.Med.Chem.Lett_10_1523
PubMedID: 10915041

Title : Probing the active center Gorge of acetylcholinesterase by fluorophores Linked to substituted cysteines - Boyd_2000_J.Biol.Chem_275_22401
Author(s) : Boyd AE , Marnett AB , Wong L , Taylor P
Ref : Journal of Biological Chemistry , 275 :22401 , 2000
Abstract : To examine the influence of individual side chains in governing rates of ligand entry into the active center gorge of acetylcholinesterase and to characterize the dynamics and immediate environment of these residues, we have conjugated reactive groups with selected charge and fluorescence characteristics to cysteines substituted by mutagenesis at specific positions on the enzyme. Insertion of side chains larger than in the native tyrosine at position 124 near the constriction point of the active site gorge confers steric hindrance to affect maximum catalytic throughput (k(cat)/K(m)) and rates of diffusional entry of trifluoroketones to the active center. Smaller groups appear not to present steric constraints to entry; however, cationic side chains selectively and markedly reduce cation ligand entry through electrostatic repulsion in the gorge. The influence of side chain modification on ligand kinetics has been correlated with spectroscopic characteristics of fluorescent side chains and their capacity to influence the binding of a peptide, fasciculin, which inhibits catalysis peripherally by sealing the mouth of the gorge. Acrylodan conjugated to cysteine was substituted for tyrosine at position 124 within the gorge, for histidine 287 on the surface adjacent to the gorge and for alanine 262 on a mobile loop distal to the gorge. The 124 position reveals the most hydrophobic environment and the largest hypsochromic shift of the emission maximum with fasciculin binding. This finding likely reflects a sandwiching of the acrylodan in the complex with the tip of fasciculin loop II. An intermediate spectral shift is found for the 287 position, consistent with partial occlusion by loops II and III of fasciculin in the complex. Spectroscopic properties of the acrylodan at the 262 position are unaltered by fasciculin addition. Hence, combined spectroscopic and kinetic analyses reveal distinguishing characteristics in various regions of acetylcholinesterase that influence ligand association.
ESTHER : Boyd_2000_J.Biol.Chem_275_22401
PubMedSearch : Boyd_2000_J.Biol.Chem_275_22401
PubMedID: 10779503

Title : Acetylcholinesterase Structural Perturbations Examined Through Cysteine Substitution Mutagenesis -
Author(s) : Boyd AE , Wong L , Taylor P
Ref : In: Structure and Function of Cholinesterases and Related Proteins - Proceedings of Sixth International Meeting on Cholinesterases , (Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. Eds) Plenum Publishing Corp. :452 , 1998
PubMedID: