Oxygen Activation by the Noncoupled Binuclear Copper Site in Peptidylglycine α-Hydroxylating Monooxygenase. Reaction Mechanism and Role of the Noncoupled Nature of the Active Site

2004 ◽  
Vol 126 (15) ◽  
pp. 4991-5000 ◽  
Author(s):  
Peng Chen ◽  
Edward I. Solomon
Keyword(s):  
Reaction Mechanism ◽  
Active Site ◽  
Oxygen Activation ◽  
Binuclear Copper ◽  
Copper Site

Nitrogen and Sulfur Transferases

2007 ◽  
Author(s):  
Perry A. Frey ◽  
Adrian D. Hegeman
Keyword(s):  
Steady State ◽  
Reaction Mechanism ◽  
Active Site ◽  
Reaction Mechanisms ◽  
Radical Reaction ◽  
Amino Group ◽  
Steady State Kinetics ◽  
Ping Pong ◽  
Polar Reaction

Unlike other group transfer reactions in biochemistry, the actions of nitrogen transferring enzymes do not follow a single unifying chemical principle. Nitrogen-transferring enzymes catalyze aminotransfer, amidotransfer, and amidinotransfer. An aminotransferase catalyzes the transfer of the NH2 group from a primary amine to a ketone or aldehyde. An amidotransferase catalyzes the transfer of the anide-NH2 group from glutamine to another group. These reactions proceed by polar reaction mechanisms. Aminomutases catalyze 1,2-intramolecular aminotransfer, in which an amino group is inserted into an adjacent C—H bond. The action of lysine 2,3-aminomutase, described in chapter 7, is an example of an aminomutase that functions by a radical reaction mechanism. Tyrosine 2,3-aminomutase also catalyzes the 2,3-amino migration, but it does so by a polar reaction mechanism. In this chapter, we consider NH2-transferring enzymes that function by polar reaction mechanisms. Transaminases or aminotransferases are the most extensively studied pyridoxal-5'-phosphate (PLP)–dependent enzymes, and many aminotransferases catalyze essential steps in catabolic and anabolic metabolism. In the classic transaminase reaction, aspartate aminotransferase (AAT) catalyzes the fully reversible reaction of L-aspartate with α-ketoglutarate according to fig. 13-1 to form oxaloacetate and L-glutamate. Like all aminotransferases, AAT is PLP dependent, and PLP functions in its classic role of providing a reactive carbonyl group to function in facilitating the cleavage of the α-H of aspartate and the departure of the α-amino group of aspartate for transfer to α-ketoglutarate (Snell, 1962). PLP in the holoenzyme functions in essence to stabilize the α-carbanions of L-aspartate or L-glutamate, the major biological role of PLP discussed in chapter 3. The functional groups of the enzyme catalyze steps in the mechanism, such as the 1,3-prototropic shift of the α-proton to C4' of pyridoxamine 5'-phosphate (PMP). The steady-state kinetics corresponds to the ping pong bi bi mechanism shown at the bottom of fig. 13-1. This mechanism allows L-aspartate to react with the internal aldimine, E=PLP in fig. 13-1, to produce an equivalent of oxaloacetate, with conversion of PLP to PMP at the active site (E.PMP), the free, covalently modified enzyme in the ping pong mechanism.

scholarly journals Viviparus ater Hemocyanin: Investigation of the Dioxygen-Binding Site and Stability of the Oxy- and Apo-Forms

2001 ◽  
Vol 56 (9-10) ◽  
pp. 843-847
Author(s):  
Dessislava Nikolova Georgieva ◽  
Stanka Stoeva ◽  
Wolfgang Voelter ◽  
Nicolay Genov
Keyword(s):  
Binding Site ◽  
Charge Distribution ◽  
Active Site ◽  
Binding Sites ◽  
Binuclear Copper ◽  
Circular Dichroism Spectra ◽  
Melting Temperatures ◽  
The Stability ◽  
Circular Dichroïsm

Abstract The active site of Viviparus ater (mollusc) hemocyanin was investigated using the fact that the binding of dioxygen to the binuclear copper-containing sites of hemocyanins is connected with the appearance of specific dichroic bands which are very sensitive to changes in the structrure and polarity of the environment. Oxy-Viviparus ater hemocyanin exhibits near UV and visible circular dichroism spectra different from those of other molluscan and arthropo-dan hemocyanins. These differences are due probably to variations in the geometry or charge distribution in the dioxygen binding sites of the compared proteins.The thermostability of Viviparus ater hemocyanin and the significance of the copper-dioxy-gen system for the stability were also investigated. “Melting” temperatures, Tm, of 77 °C for the oxy-hemocyanin and 57 °C for the apo-protein were calculated from the denaturation curves which demonstrates the considerable role of the binuclear active site for the thermostability. Viviparus ater hemocyanin is more thermostable than other hemocyanins for which data are published.

scholarly journals Temporary Intermediates of L-Trp Along the Reaction Pathway of Human Indoleamine 2,3-Dioxygenase 1 and Identification of an Exo Site

2021 ◽  
Vol 14 ◽  
pp. 117864692110529
Author(s):  
Manon Mirgaux ◽  
Laurence Leherte ◽  
Johan Wouters
Keyword(s):  
Molecular Dynamics ◽  
Reaction Mechanism ◽  
Crystal Structures ◽  
Protein Dynamics ◽  
Active Site ◽  
Reaction Pathway ◽  
Small Unit ◽  
Indoleamine 2,3 Dioxygenase ◽  
Dynamics Simulations

Protein dynamics governs most of the fundamental processes in the human body. Particularly, the dynamics of loops located near an active site can be involved in the positioning of the substrate and the reaction mechanism. The understanding of the functioning of dynamic loops is therefore a challenge, and often requires the use of a multi-disciplinary approach mixing, for example, crystallographic experiments and molecular dynamics simulations. In the present work, the dynamic behavior of the JK-loop of the human indoleamine 2,3-dioxygenase 1 hemoprotein, a target for immunotherapy, is investigated. To overcome the lack of knowledge on this dynamism, the study reported here is based on 3 crystal structures presenting different conformations of the loop, completed with molecular dynamics trajectories and MM-GBSA analyses, in order to trace the reaction pathway of the enzyme. In addition, the crystal structures identify an exo site in the small unit of the enzyme, that is populated redundantly by the substrate or the product of the reaction. The role of this newer reported exo site still needs to be investigated.

Spectroscopic and Density Functional Studies of the Red Copper Site in Nitrosocyanin:  Role of the Protein in Determining Active Site Geometric and Electronic Structure

2005 ◽  
Vol 127 (10) ◽  
pp. 3531-3544 ◽  
Author(s):  
Lipika Basumallick ◽  
Ritimukta Sarangi ◽  
Serena DeBeer George ◽  
Brad Elmore ◽  
Alan B. Hooper ◽  
...  
Keyword(s):  
Electronic Structure ◽  
Active Site ◽  
Density Functional ◽  
Functional Studies ◽  
Copper Site

scholarly journals Role of Active Site Water Molecules and Substrate Hydroxyl Groups in Oxygen Activation by Cytochrome P450 158A2

2005 ◽  
Vol 280 (51) ◽  
pp. 42188-42197 ◽  
Author(s):  
Bin Zhao ◽  
F. Peter Guengerich ◽  
Markus Voehler ◽  
Michael R. Waterman
Keyword(s):  
Cytochrome P450 ◽  
Active Site ◽  
Oxygen Activation ◽  
Water Molecules ◽  
Hydroxyl Groups ◽  
Site Water
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