The Crystal Structure of Benzoylformate Decarboxylase at 1.6 Å Resolution:  Diversity of Catalytic Residues in Thiamin Diphosphate-Dependent Enzymes†,‡

Biochemistry ◽  
1998 ◽  
Vol 37 (28) ◽  
pp. 9918-9930 ◽  
Author(s):  
Miriam S. Hasson ◽  
Angelika Muscate ◽  
Michael J. McLeish ◽  
Lena S. Polovnikova ◽  
John A. Gerlt ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Thiamin Diphosphate ◽  
Catalytic Residues ◽  
Benzoylformate Decarboxylase

scholarly journals Inhibition and Crystal Structure of the Human DHTKD1-Thiamin Diphosphate Complex

2020 ◽  
Vol 15 (8) ◽  
pp. 2041-2047 ◽  
Author(s):  
João Leandro ◽  
Susmita Khamrui ◽  
Hui Wang ◽  
Chalada Suebsuwong ◽  
Natalia S. Nemeria ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Thiamin Diphosphate

scholarly journals Structural insights into bifunctional thaumarchaeal crotonyl-CoA hydratase and 3-hydroxypropionyl-CoA dehydratase from Nitrosopumilus maritimus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ebru Destan ◽  
Busra Yuksel ◽  
Bradley B. Tolar ◽  
Esra Ayan ◽  
Sam Deutsch ◽  
...  
Keyword(s):  
Crystal Structure ◽  
High Resolution ◽  
Energy Efficient ◽  
Bifunctional Enzyme ◽  
Catalytic Residues ◽  
Structural Insights ◽  
Essential Reactions

AbstractThe ammonia-oxidizing thaumarchaeal 3-hydroxypropionate/4-hydroxybutyrate (3HP/4HB) cycle is one of the most energy-efficient CO2 fixation cycles discovered thus far. The protein encoded by Nmar_1308 (from Nitrosopumilus maritimus SCM1) is a promiscuous enzyme that catalyzes two essential reactions within the thaumarchaeal 3HP/4HB cycle, functioning as both a crotonyl-CoA hydratase (CCAH) and 3-hydroxypropionyl-CoA dehydratase (3HPD). In performing both hydratase and dehydratase activities, Nmar_1308 reduces the total number of enzymes necessary for CO2 fixation in Thaumarchaeota, reducing the overall cost for biosynthesis. Here, we present the first high-resolution crystal structure of this bifunctional enzyme with key catalytic residues in the thaumarchaeal 3HP/4HB pathway.

Crystal Structure of Haloalkane Dehalogenase LinB fromSphingomonas paucimobilisUT26 at 0.95 Å Resolution:  Dynamics of Catalytic Residues†,‡

Biochemistry ◽  
2004 ◽  
Vol 43 (4) ◽  
pp. 870-878 ◽  
Author(s):  
Aaron J. Oakley ◽  
Martin Klvaňa ◽  
Michal Otyepka ◽  
Yuji Nagata ◽  
Matthew C. J. Wilce ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Haloalkane Dehalogenase ◽  
Catalytic Residues

scholarly journals Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

2019 ◽  
Vol 15 ◽  
pp. 145-159 ◽  
Author(s):  
Ferran Planas ◽  
Michael J McLeish ◽  
Fahmi Himo
Keyword(s):  
Density Functional ◽  
Density Functional Theory Calculations ◽  
Thiamin Diphosphate ◽  
Diverse Range ◽  
Factors Affecting ◽  
Benzoylformate Decarboxylase ◽  
Carbon Carbon Bond ◽  
Activated State ◽  
Catalyzed Reactions ◽  
The Individual

Thiamin diphosphate (ThDP)-dependent enzymes constitute a large class of enzymes that catalyze a diverse range of reactions. Many are involved in stereospecific carbon–carbon bond formation and, consequently, have found increasing interest and utility as chiral catalysts in various biocatalytic applications. All ThDP-catalyzed reactions require the reaction of the ThDP ylide (the activated state of the cofactor) with the substrate. Given that the cofactor can adopt up to seven states on an enzyme, identifying the factors affecting the stability of the pre-reactant states is important for the overall understanding of the kinetics and mechanism of the individual reactions. In this paper we use density functional theory calculations to systematically study the different cofactor states in terms of energies and geometries. Benzoylformate decarboxylase (BFDC), which is a well characterized chiral catalyst, serves as the prototypical ThDP-dependent enzyme. A model of the active site was constructed on the basis of available crystal structures, and the cofactor states were characterized in the presence of three different ligands (crystallographic water, benzoylformate as substrate, and (R)-mandelate as inhibitor). Overall, the calculations reveal that the relative stabilities of the cofactor states are greatly affected by the presence and identity of the bound ligands. A surprising finding is that benzoylformate binding, while favoring ylide formation, provided even greater stabilization to a catalytically inactive tricyclic state. Conversely, the inhibitor binding greatly destabilized the ylide formation. Together, these observations have significant implications for the reaction kinetics of the ThDP-dependent enzymes, and, potentially, for the use of unnatural substrates in such reactions.

Mechanism-Based Inactivation of Benzoylformate Decarboxylase, A Thiamin Diphosphate-Dependent Enzyme

2007 ◽  
Vol 129 (14) ◽  
pp. 4120-4121 ◽  
Author(s):  
Asim K. Bera ◽  
Lena S. Polovnikova ◽  
Juliatek Roestamadji ◽  
Theodore S. Widlanski ◽  
George L. Kenyon ◽  
...  
Keyword(s):  
Thiamin Diphosphate ◽  
Benzoylformate Decarboxylase

scholarly journals The Crystal Structure of Nα-p-tosyl-lysyl Chloromethylketone-Bound Oligopeptidase B from Serratia Proteamaculans Revealed a New Type of Inhibitor Binding

Crystals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1438
Author(s):  
Vladimir I. Timofeev ◽  
Dmitry E. Petrenko ◽  
Yulia K. Agapova ◽  
Anna V. Vlaskina ◽  
David M. Karlinsky ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Pocket ◽  
Catalytic Triad ◽  
Inhibitor Binding ◽  
Inhibitor Molecule ◽  
Covalent Bonds ◽  
Catalytic Residues ◽  
Serratia Proteamaculans ◽  
Oligopeptidase B ◽  
New Type

A covalent serine protease inhibitor—Na-p-tosyl-lysyl chloromethylketone (TCK) is a modified lysine residue tosylated at the N-terminus and chloromethylated at the C-terminus, one molecule of which is capable of forming two covalent bonds with both Ser and His catalytic residues, was co-crystallized with modified oligopeptidase B (OpB) from Serratia proteomaculans (PSPmod). The kinetics study, which preceded crystallization, shows that the stoichiometry of TCK-dependent inhibition of PSPmod was 1:2 (protein:inhibitor). The crystal structure of the PSPmod-TCK complex, solved at a resolution of 2.3 Å, confirmed a new type of inhibitor binding. Two TCK molecules were bound to one enzyme molecule: one with the catalytic Ser, the other with the catalytic His. Due to this mode of binding, the intermediate state of PSPmod and the disturbed conformation of the catalytic triad were preserved in the PSPmod-TCK complex. Nevertheless, the analysis of the amino acid surroundings of the inhibitor molecule bound to the catalytic Ser and its comparison with that of antipain-bound OpB from Trypanosoma brucei provided an insight in the structure of the PSPmod substrate-binding pocket. Supposedly, the new type of binding is typical for the interaction of chloromethylketone derivatives with two-domain OpBs. In the open conformational state that these enzymes are assumed in solution, the disordered configuration of the catalytic triad prevents simultaneous interaction of one inhibitor molecule with two catalytic residues.

Structural and Kinetic Analysis of Catalysis by a Thiamin Diphosphate-Dependent Enzyme, Benzoylformate Decarboxylase†

Biochemistry ◽  
2003 ◽  
Vol 42 (7) ◽  
pp. 1820-1830 ◽  
Author(s):  
Elena S. Polovnikova ◽  
Michael J. McLeish ◽  
Eduard A. Sergienko ◽  
John T. Burgner ◽  
Natalie L. Anderson ◽  
...  
Keyword(s):  
Kinetic Analysis ◽  
Thiamin Diphosphate ◽  
Benzoylformate Decarboxylase
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