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Histidine flipping

The flipped orientation of the heme in HPII and PVC results in the oxidized ring being sufficiently well removed (7 A) from the essential histidine (His 128 in HPII) and the presumed peroxide binding site to complicate an explanation of the reaction mechanism. The explanation is further complicated by the cis-stereospecificity of the reaction that results in both oxygens being situated on the proximal side of the heme away from what is considered to be the normal reaction center on the distal side. This stereochemistry dictates that the hydroxyl group on the heme d have originated on the proximal side of the heme, and a mechanism has been proposed to explain the reaction in both PVC and HPII 93). The mechanism assumes that compound I is formed as a first step... [Pg.84]

Fig. 13. Active site residues in a small-subunit catalase BLC (A) and a large-subunit catalase HPIl (B). The active site residues are labeled, and hydrogen bonds are shown between the serine (113 in BLC and 167 in HPll) and the essential histidine (74 in BLC and 128 in HPll). A single water is shown hydrogen bonded to the histidine. The equivalent water in BLC is located by analogy to the position of the water in HPll. The unusual covalent bond between the N of His392 and the C of Tyr415 in HPll is evident on the proximal side of the heme in B. The flipped orientations of the hemes are evident in a comparison of the two structures, as is the eis-hydroxyspirolactone structure of heme d in B. Fig. 13. Active site residues in a small-subunit catalase BLC (A) and a large-subunit catalase HPIl (B). The active site residues are labeled, and hydrogen bonds are shown between the serine (113 in BLC and 167 in HPll) and the essential histidine (74 in BLC and 128 in HPll). A single water is shown hydrogen bonded to the histidine. The equivalent water in BLC is located by analogy to the position of the water in HPll. The unusual covalent bond between the N of His392 and the C of Tyr415 in HPll is evident on the proximal side of the heme in B. The flipped orientations of the hemes are evident in a comparison of the two structures, as is the eis-hydroxyspirolactone structure of heme d in B.
Indeed, the presence of a hydroxamic acid improved the potency two- to three fold (14). However, after solving the cocrystal structure of 14 it was found that this improvement was not due to the expected zinc coordination (not shown). Inhibitor 14 flipped by 180° compared to inhibitor 13 and, as a consequence, the hydroxamic acid was located at the bottom of the GGPP binding pocket. Instead, histidine AA coordinated to the zinc ion, suggesting that it might be possible to target the reactive center of the active site. [Pg.193]

During the course of the structure validation project, we have discovered about one class of errors every 2 weeks. Most of these errors are fully unimportant to the average PDB-file user, but they are errors nonetheless. Consequently, it is impossible even to list all types of errors here. In this chapter, we have to limit ourselves to a discussion of a few classes of errors that, if not detected, could severely hamper the scientist who bases an experiment on a three-dimensional structure. We will discuss flipping of asparagine, histidine, and glutamine side-chains, administration of alternate atoms and residues, and the role of water molecules in protein structures. A large class of error types is formed by nomenclature errors. Table 3 lists some nomenclature errors we found in the PDB. [Pg.396]

Figure 4.1 shows the effect of resolution on the electron density for histidine residues in three kinase protein structures of varying resolution. In the highly resolved structure, the density reveals the clear shape of a histidine one can resolve atomic centers in the density. In the less well-resolved structures, the interpretation is more subjective. Even in the high-resolution structure, a flip around the exocyclic bond would still yield a model that fitted to the density reasonably well. [Pg.88]

Catalysis by (6—4) photolyase must accomplish two chemical tasks cleavage of the C6—C4 sig a bond, and transfer of the OH (or —NH2) group from the C5 of the 5 base to the G4 of the 3 base. Because formation of the (6—4) photoproduct is presumed to proceed through a four-mem-bered oxetane or azetidine intermediate, it has been proposed that (6—4) photolyase first converts the open form of the (6—4) photoproduct to the four-membered ring by a thermal reaction, and then the four-mem-bered ring is cleaved by retro [2+2] reaction photochemically (Kim et al, 1994 Zhao et aL, 1997). A site-directed mutagenesis study has identified two histidine residues in the active site that may participate in conversion of the (6-4) photoproduct to the oxetane intermediate by general acid-base catalysis (Hitomi et al, 2001). A current model for catalysis by (6-4) photolyase is as follows (Fig. 8) The enzyme binds DNA and flips out the... [Pg.88]

The largest decrease in the interfacial tension is exhibited by the unsaturated amino acid L-tryptophan [91]. Tryptophan is adsorbed at full coverage in the perpendicular position except at the lowest concentration, whereas histidine is adsorbed planar at concentration below 0.05 M and flips up as molecules pack in at higher concentrations. Tyrosine, cystine, lysine, and methionine adsorb in the planar configuration [92]. [Pg.315]


See other pages where Histidine flipping is mentioned: [Pg.159]    [Pg.67]    [Pg.396]    [Pg.247]    [Pg.159]    [Pg.67]    [Pg.396]    [Pg.247]    [Pg.464]    [Pg.465]    [Pg.48]    [Pg.56]    [Pg.158]    [Pg.158]    [Pg.112]    [Pg.66]    [Pg.150]    [Pg.11]    [Pg.2306]    [Pg.1759]    [Pg.77]    [Pg.78]    [Pg.79]    [Pg.16]    [Pg.272]    [Pg.396]    [Pg.396]    [Pg.397]    [Pg.91]    [Pg.92]    [Pg.101]    [Pg.179]    [Pg.195]    [Pg.385]    [Pg.141]    [Pg.1079]    [Pg.1089]    [Pg.140]    [Pg.66]    [Pg.32]   
See also in sourсe #XX -- [ Pg.396 ]




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