Peroxidases crystal structures

Bertrand T, NAJ Eady, IN Jones, Jesmin, JM Nagy, B Jamart-Gregoire, EL Raven, KA Brown (2004) Crystal structure of Mycobacterium tuberculosis catalase-peroxidase. J Biol Chem 279 38991-38999. 

The catalase-peroxidases present other challenges. More than 20 sequences are available, and interest in the enzyme arising from its involvement in the process of antihiotic sensitivity in tuherculosis-causing bacteria has resulted in a considerable body of kinetic and physiological information. Unfortunately, the determination of crystallization conditions and crystals remain an elusive goal, precluding the determination of a crystal structure. Furthermore, the presence of two possible reaction pathways, peroxidatic and catalatic, has complicated a definition of the reaction mechanisms and the identity of catalytic intermediates. There is work here to occupy biochemists for many more years. 

Fig. 6. Mechanisms for the reduction of compounds I and II of HRP C by ferulic acid, after Henriksen et al. 195). This scheme is based on new information from the 1.45 A resolution crystal structure of the ternary complex of ferulic acid and cyanide-ligated HRP C 195). The direction of proton transfer is indicated by the dotted arrows. The mechanism is discussed in Section IV,B,2, and the crystal structure data in Section IV,F,4. Note that a distal site water molecule makes an important hydrogen bond with the backbone carbonyl group of Prol39 (a residue conserved in all members of the plant peroxidase superfamily).

The crystal structures of two ferulic acid complexes of HRP C have been solved, one with resting state enzyme (to 2.0 A resolution) and the other with the cyanide-ligated enzyme (to 1.45 A resolution) 195). These represent a major achievement for the crystallography of peroxidase complexes. The binary complex is heterogenous, according to the 2Fo-Fc omit difference electron density map of the active site. The disordered density observed has been interpreted in terms of three... 

Most well-studied peroxidases are designed to oxidize small aromatic molecules, with the exception of cytochrome c peroxidase. It generally is thought that such aromatic molecules bind near the heme edge where an electron can transfer directly to the heme edge (44), which is supported by both crystal structures (45, 46) and NMR studies (47). However, recent work suggests that some physiologically important substrates may utilize other sites on the enzyme surface (48, 49). 

Various isoforms of both HO and NOS can be expressed in recombinant systems. As a result, the immediate future will undoubtedly witness a wealth of mutagenesis experiments guided by the crystal structures. It also may be possible to trap in crystalline form the various intermediates of the HO reaction cycle, which will greatly facilitate a deeper understanding of the catalytic mechanism. Conformational dynamics appear to be quite important in HO, and hence, a variety of spectral probes such as NMR and fluorescence should prove especially useful in studying the role of protein dynamics in function. Overall there should be considerable optimism for understanding HO at the level of detail achieved for peroxidases and other well-studied enz5une systems. 

Crystal structures of manganese catalases (in the (111)2 oxidation state) from Lactobacillus plantarum,its azide-inhibited complex, " and from Thermus thermophilus have been determined. There are differences between the structures that may reflect distinct biological functions for the two enzymes, the L. plantarum enzyme functions only as a catalase, while the T. thermo-philus enzyme may function as a catalase/peroxidase. The active sites are conserved in the two enzymes and are shown schematically in Figure 32. Each subunit contains an Mu2 active site,... 

Fig. 10 X-ray co-crystal structure of praziquantel 211 and glutathione-S-peroxidase complex (PDB ID IGTB). Praziquantel is shown as yellow sticks and the receptor binding site is shown as hydrophobic surface...

Arthritis, gold antiarthritic drugs, 36 17-23 Arthromyces ramosus peroxidase, 43 79 active-site structure, 43 85, 87 crystal structure, 43 84-87 residue location, 43 101-102 van der Waals surfaces, 43 112-113 Aryl... 

Jin S, Kurtz DM, Liu ZJ, Rose J, Wang BC (2002) X-ray crystal structures of reduced rubr-erythrin and its azide adduct a structure-based mechanism for a non-heme diiron peroxidase. J Am Chem Soc 124 9845-9855... 

Sundaramoorthy M, Temer J, Poulos TL (1995) The Crystal Structure of Chloroperoxidase A Heme Peroxidase-Cytochrome P450 Functional Hybrid. Structure 3 1367... 

New insights into the peroxide binding and in the catalysis, obtained through site-directed mutagenesis, have led to much-improved understanding of heme peroxidases and their possible applications. New crystal structures of peroxidases have provided much more information on the local heme environments [32],... 

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