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Structure and Mechanism of Metalloenzyme Active Sites

In dealing with such a vast domain some decisions concerning the subjects addressed in this short chapter had to be made. Consequently, only selected enzymes containing the transition metals copper, iron, manganese, molybdenum/ tungsten, nickel and the related zinc, will be discussed also, we will consider only X-ray structures of active sites published relatively recently and for which some discussion on the catalytic mechanism is included. Some reference is also made to Co in the context of the correnoid iron sulfur protein that interacts with acetyl Coenzyme A synthase in the synthesis or cleavage of acetyl CoA. With a few exceptions, the protein structure beyond the metal coordination sphere will not be described unless it impinges in the catalytic mechanism. [Pg.353]

There are complicating factors when studying metalloenzymes. In many instances, metal sites seem to be rather indiscriminating, at least in vitro, as different ions can bind to them with various degrees of residual catalytic activity this makes it difficult to establish which is the physiologically relevant metal. [Pg.353]

The chapter is organized in sections according to the various metal ions and representative members are discussed in each case, in terms of active site structure and catalytic mechanisms. [Pg.354]


J801 J J Structure and Mechanism of Metalloenzyme Active Sites... [Pg.380]

Metalloenzymes pose a particular problem to both experimentalists and modelers. Crystal structures of metalloenzymes typically reveal only one state of the active site and the state obtained frequently depends on the crystallization conditions. In some cases, states probably not relevant to any aspect of the mechanism have been obtained, and in many cases it may not be possible to obtain states of interest, simply because they are too reactive. This is where molecular modeling can make a unique contribution and a recent study of urease provides a good example of what can be achieved119 1. A molecular mechanics study of urease as crystallized revealed that a water molecule was probably missing from the refined crystal structure. A conformational search of the active site geometry with the natural substrate, urea, bound led to the determination of a consensus binding model[I91]. Clearly, the urea complex cannot be crystallized because of the rate at which the urea is broken down to ammonia and, therefore, modeling approaches such as this represent a real contribution to the study of metalloenzymes. [Pg.164]

Metalloenzymes with non-heme di-iron centers in which the two irons are bridged by an oxide (or a hydroxide) and carboxylate ligands (glutamate or aspartate) constitute an important class of enzymes. Two of these enzymes, methane monooxygenase (MMO) and ribonucleotide reductase (RNR) have very similar di-iron active sites, located in the subunits MMOH and R2 respectively. Despite their structural similarity, these metal centers catalyze very different chemical reactions. We have studied the enzymatic mechanisms of these enzymes to understand what determines their catalytic activity [24, 25, 39-41]. [Pg.34]

Despite the fact that carbonic anhydrase was the first zinc metalloenzyme identified1233 and a good deal is known of its structure, there is still controversy about the nature of the various active-site species and the detailed mechanisms of their action. In particular, the identity of the group with a pXa of 7 that is involved in the mechanism, and the stereochemistry around the zinc ion during catalysis, are still in dispute. The various mechanisms proposed assume either ionization of a histidine imidazole group (bound or not to the zinc) and nucleophilic attack on C02 by the coordinated imidazolate anion,1273,1274 or ionization of the Znn-coordinated water and nucleophilic attack on C02 by OH. 1271 Many papers on this problem have appeared recently and the extensive literature is the subject of the several review articles referred to above. [Pg.1004]

Thus, many metal ions catalyze the hydrolysis of esters [7,8], amides [9], and nitriles [10] via electrophilic activation of the C=0 or C=N group. This type of catalysis is characteristic of coordination complexes and is very common in metalloenzyme-mediated processes. Zinc(II), for example, is a key structural component of more than 300 enzymes, in which its primary function is to act as a Lewis acid (see Chapter 4). The mechanism of action of zinc proteases, e.g., thermolysin, involves electrophilic activation of an amide carbonyl group by coordination to zinc(II) in the active site (Figure 4). [Pg.16]

Roughly 30% of enzymes are metalloenzymes or require metal ions for activity and the present chapter will concentrate on the chemisty and structure of the plant metalloenzymes. As analytical methods have improved it has been possible to establish a metal ion requirement for a variety of enzymes which were initially considered to be pure proteins. A dramatic example is provided by the enzyme urease isolated from Jack beans and first crystallised by Sumner (1926) (the first enzyme to be crystallised). Sumner defined an enzyme as a pure protein with catalytic activity, however, Zerner and his coworkers (Dixon et al., 1975) established that urease is in fact a nickel metalloenzyme. Jack bean urease contains two moles of nickel(II) per mole of active sites and at least one of these metal ions is implicated in its mechanism of action. [Pg.108]

Cao ZX, Hall MB. Modeling the active sites in metalloenzymes. 3. Density functional calculations on models for [Fe]-hydrogenase structures and vibrational frequencies of the observed redox forms and the reaction mechanism at the diiron active center. J Am Chem Soc. 2001 123(16) 3734-42. [Pg.222]

N-substituted iron porphyrins form upon treatment of heme enzymes with many xenobiotics. The formation of these modified hemes is directly related to the mechanism of their enzymatic reactivity. N-alkyl porphyrins may be formed from organometallic iron porphyrin complexes, PFe-R (a-alkyl, o-aryl) or PFe = CR2 (carbene). They are also formed via a branching in the reaction path used in the epoxidation of alkenes. Biomimetic N-alkyl porphyrins are competent catalysts for the epoxidation of olefins, and it has been shown that iron N-alkylporphyrins can form highly oxidized species such as an iron(IV) ferryl, (N-R P)Fe v=0, and porphyrin ir-radicals at the iron(III) or iron(IV) level of metal oxidation. The N-alkylation reaction has been used as a low resolution probe of heme protein active site structure. Modified porphyrins may be used as synthetic catalysts and as models for nonheme and noniron metalloenzymes. [Pg.376]


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Activation mechanism

Active site mechanism

Active sites structures

Mechanical activity

Mechanical structure

Mechanism of activation

Metalloenzyme

Metalloenzyme active site

Metalloenzymes

Metalloenzymes activation

Site Structure

Site structural

Structural mechanic

Structural mechanism

Structure activity, and

Structure and mechanical

Structure of active sites

Structure, and mechanism

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