An Essential Role for Water in an Enzyme Reaction Mechanism:  The Crystal Structure of the Thymidylate Synthase Mutant E58Q†,‡

Biochemistry ◽  
1996 ◽  
Vol 35 (50) ◽  
pp. 16270-16281 ◽  
Author(s):  
Carleton R. Sage ◽  
Earl E. Rutenber ◽  
Thomas J. Stout ◽  
Robert M. Stroud
Keyword(s):  
Crystal Structure ◽  
Reaction Mechanism ◽  
Thymidylate Synthase ◽  
Essential Role ◽  
Enzyme Reaction

Crystal Structure of Bacillus sp. GL1 Xanthan Lyase Complexed with a Substrate: Insights into the Enzyme Reaction Mechanism

2005 ◽  
Vol 350 (5) ◽  
pp. 974-986 ◽  
Author(s):  
Yukie Maruyama ◽  
Wataru Hashimoto ◽  
Bunzo Mikami ◽  
Kousaku Murata
Keyword(s):  
Crystal Structure ◽  
Reaction Mechanism ◽  
Enzyme Reaction ◽  
Bacillus Sp

The crystal structure of human mitochondrial 3-ketoacyl-CoA thiolase (T1): insight into the reaction mechanism of its thiolase and thioesterase activities

2014 ◽  
Vol 70 (12) ◽  
pp. 3212-3225 ◽  
Author(s):  
Tiila-Riikka Kiema ◽  
Rajesh K. Harijan ◽  
Malgorzata Strozyk ◽  
Toshiyuki Fukao ◽  
Stefan E. H. Alexson ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Reaction Mechanism ◽  
Active Site ◽  
Quaternary Structure ◽  
Fatty Acyl ◽  
Physiological Importance ◽  
Loop Domain ◽  
Solution Studies ◽  
Hydrolysis Of ◽  
Insight Into

Crystal structures of human mitochondrial 3-ketoacyl-CoA thiolase (hT1) in the apo form and in complex with CoA have been determined at 2.0 Å resolution. The structures confirm the tetrameric quaternary structure of this degradative thiolase. The active site is surprisingly similar to the active site of theZoogloea ramigerabiosynthetic tetrameric thiolase (PDB entries 1dm3 and 1m1o) and different from the active site of the peroxisomal dimeric degradative thiolase (PDB entries 1afw and 2iik). A cavity analysis suggests a mode of binding for the fatty-acyl tail in a tunnel lined by the Nβ2–Nα2 loop of the adjacent subunit and the Lα1 helix of the loop domain. Soaking of the apo hT1 crystals with octanoyl-CoA resulted in a crystal structure in complex with CoA owing to the intrinsic acyl-CoA thioesterase activity of hT1. Solution studies confirm that hT1 has low acyl-CoA thioesterase activity for fatty acyl-CoA substrates. The fastest rate is observed for the hydrolysis of butyryl-CoA. It is also shown that T1 has significant biosynthetic thiolase activity, which is predicted to be of physiological importance.

scholarly journals Crystal structure of the yeast His6 enzyme suggests a reaction mechanism

2006 ◽  
Vol 15 (6) ◽  
pp. 1516-1521 ◽  
Author(s):  
Sophie Quevillon-Cheruel ◽  
Nicolas Leulliot ◽  
Marc Graille ◽  
Karine Blondeau ◽  
Joel Janin ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Reaction Mechanism

Design, Synthesis, and X-ray Crystal Structure of a Potent Dual Inhibitor of Thymidylate Synthase and Dihydrofolate Reductase as an Antitumor Agent1

2000 ◽  
Vol 43 (21) ◽  
pp. 3837-3851 ◽  
Author(s):  
Aleem Gangjee ◽  
Jianming Yu ◽  
John J. McGuire ◽  
Vivian Cody ◽  
Nikolai Galitsky ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Dihydrofolate Reductase ◽  
Thymidylate Synthase ◽  
Dual Inhibitor ◽  
Design Synthesis ◽  
X Ray

The Crystal Structure of RosB: Insights into the Reaction Mechanism of the First Member of a Family of Flavodoxin-like Enzymes

2016 ◽  
Vol 56 (4) ◽  
pp. 1146-1151 ◽  
Author(s):  
Valentino Konjik ◽  
Steffen Brünle ◽  
Ulrike Demmer ◽  
Amanda Vanselow ◽  
Roger Sandhoff ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Reaction Mechanism

The crystal structure of thymidylate synthase from Pneumocystis carinii reveals a fungal insert important for drug design

2000 ◽  
Vol 297 (3) ◽  
pp. 645-657 ◽  
Author(s):  
Amy C Anderson ◽  
Kathy M Perry ◽  
Douglas M Freymann ◽  
Robert M Stroud
Keyword(s):  
Crystal Structure ◽  
Drug Design ◽  
Thymidylate Synthase ◽  
Pneumocystis Carinii

scholarly journals Divergent architecture of the heterotrimeric NatC complex explains N-terminal acetylation of cognate substrates

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephan Grunwald ◽  
Linus V. M. Hopf ◽  
Tobias Bock-Bierbaum ◽  
Ciara C. M. Lally ◽  
Christian M. T. Spahn ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Essential Role ◽  
Catalytic Mechanism ◽  
Detailed Structure ◽  
Auxiliary Subunits ◽  
Target Proteins ◽  
Ribosome Binding ◽  
Specific Ligand

Abstract The heterotrimeric NatC complex, comprising the catalytic Naa30 and the two auxiliary subunits Naa35 and Naa38, co-translationally acetylates the N-termini of numerous eukaryotic target proteins. Despite its unique subunit composition, its essential role for many aspects of cellular function and its suggested involvement in disease, structure and mechanism of NatC have remained unknown. Here, we present the crystal structure of the Saccharomyces cerevisiae NatC complex, which exhibits a strikingly different architecture compared to previously described N-terminal acetyltransferase (NAT) complexes. Cofactor and ligand-bound structures reveal how the first four amino acids of cognate substrates are recognized at the Naa30–Naa35 interface. A sequence-specific, ligand-induced conformational change in Naa30 enables efficient acetylation. Based on detailed structure–function studies, we suggest a catalytic mechanism and identify a ribosome-binding patch in an elongated tip region of NatC. Our study reveals how NAT machineries have divergently evolved to N-terminally acetylate specific subsets of target proteins.

Structure of the bovine COPI δ subunit μ homology domain at 2.15 Å resolution

2015 ◽  
Vol 71 (6) ◽  
pp. 1328-1334 ◽  
Author(s):  
Avital Lahav ◽  
Haim Rozenberg ◽  
Anna Parnis ◽  
Dan Cassel ◽  
Noam Adir
Keyword(s):  
Crystal Structure ◽  
Essential Role ◽  
Structural Similarity ◽  
Binding Specificity ◽  
Potential Effect ◽  
Eukaryotic Cells ◽  
Asymmetric Unit ◽  
Β Sheets ◽  
Secretory System ◽  
Structural Homologue

The heptameric COPI coat (coatomer) plays an essential role in vesicular transport in the early secretory system of eukaryotic cells. While the structures of some of the subunits have been determined, that of the δ-COP subunit has not been reported to date. The δ-COP subunit is part of a subcomplex with structural similarity to tetrameric clathrin adaptors (APs), where δ-COP is the structural homologue of the AP μ subunit. Here, the crystal structure of the μ homology domain (MHD) of δ-COP (δ-MHD) obtained by phasing using a combined SAD–MR method is presented at 2.15 Å resolution. The crystallographic asymmetric unit contains two monomers that exhibit short sections of disorder, which may allude to flexible regions of the protein. The δ-MHD is composed of two subdomains connected by unstructured linkers. Comparison between this structure and those of known MHD domains from the APs shows significant differences in the positions of specific loops and β-sheets, as well as a more general change in the relative positions of the protein subdomains. The identified difference may be the major source of cargo-binding specificity. Finally, the crystal structure is used to analyze the potential effect of the I422T mutation in δ-COP previously reported to cause a neurodegenerative phenotype in mice.

Structural basis for the interaction of BamB with the POTRA3–4 domains of BamA

2016 ◽  
Vol 72 (2) ◽  
pp. 236-244 ◽  
Author(s):  
Zhen Chen ◽  
Li-Hong Zhan ◽  
Hai-Feng Hou ◽  
Zeng-Qiang Gao ◽  
Jian-Hua Xu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Escherichia Coli ◽  
Outer Membrane ◽  
Essential Role ◽  
Biochemical Analysis ◽  
Hydrophobic Interactions ◽  
Outer Membrane Proteins ◽  
Structural Basis ◽  
Conserved Residues ◽  
Bam Complex

InEscherichia coli, the Omp85 protein BamA and four lipoproteins (BamBCDE) constitute the BAM complex, which is essential for the assembly and insertion of outer membrane proteins into the outer membrane. Here, the crystal structure of BamB in complex with the POTRA3–4 domains of BamA is reported at 2.1 Å resolution. Based on this structure, the POTRA3 domain is associated with BamBviahydrogen-bonding and hydrophobic interactions. Structural and biochemical analysis revealed that the conserved residues Arg77, Glu127, Glu150, Ser167, Leu192, Leu194 and Arg195 of BamB play an essential role in interaction with the POTRA3 domain.

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