Distal region pocket

As in the other members of the superfamily, the heme pocket of ligninolytic peroxidases includes two conserved histidine residues disposed above and below the heme plane (Fig. 3.4a). The second histidine acts as the fifth ligand of the heme iron, occupying a proximal position, while the first one is at a higher distance being, therefore, called distal histidine (by extension, the regions located below and above the heme plane are also called proximal and distal regions). 

The second region is the antiparallel (3-barrel (Fig. 8) forming the core of the subunit. It includes about 250 residues from the essential histidine toward the C-terminus. The first four strands ((31-4) are contiguous and are separated from the second four strands ((35-6) by three helices ( 3-5). The first four strands form the distal side of the heme pocket and portions of the second four strands participate in binding NADPH in small subunit enzymes. 

Conspicuously absent in HO-1 is any residue analogous to the globin and peroxidase distal His that can directly interact with iron-linked ligands. Nevertheless, the HO-1 distal pocket is polar (Fig. 20) with the potential for diatomic ligands to interact with the kinked region of the distal helix, as well as water molecules that could bridge between... 

Although the three remaining subsites of the PPAR LED exhibited less variation than the distal pockets, the CRID/CPCA calculations revealed some scope for selective interactions, in particular with the OH and C3 probes within the linker and head regions. This analysis agreed well with site-directed mutagenesis experiments, as well as the selectivity of known inhibitors. 

Fig. 7.2 Thrombin active site regions as defined by the binding of D-Phe-Pro-Arg analogues, e.g., PPACK. The recognition pocket (SI) is clear. The proximal (P) hydrophobic pocket binds the proline side chain and thus corresponds to S2. The distal (D) hydrophobic pocket binds the D-Phe side chain. For PPACK 1 Rl= CO.CHjCI.

The following abbreviations were used S3, S2, SI, ST, and S2 are the conventional labels for the HlV l protease binding site pocket (Ref. 11) for example, SI and ST are located at the catalytic site (binding the proximal and distal side chains from the scissile bond). Amino acid residues in the vicinity of the CoMFA region are numbered as in HlV-1 protease. Detrimental contributions indicated by beneficial contributions by +. Double minus or double plus mean very detrimental or beneficial, respectively. Up, down, front, and back refer qualitatively to the binding site as conveniently viewed see Ref. 122. One-letter notation for amino acids ... 

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