Discovering critical residues in glutathione reductase - Gentoo

More documents

Recommendations

Info

Figure 7: Catalytic residues His467' and Glu472'. See text for discussion The catalytic His467' and Glu472' are on the opposite end of the protein from the active site, because they participate in the active site of the other dimer. One can see that the carboxyl group of Glu472' is about 3A from the imidazole ring of histidine, with one oxygen at 2.8A and another at 3.2A (Figure 7). Also, Pro468' is highly conserved because it allows for one of the two cis peptide bonds in the protein, which is required for the correct conformation of histidine and glutamate. Thr469' and Glu473' are conserved as well, but their roles are unclear without analysis of the entire dimer with them in the active site. Their negative charges could keep Glu472' near the histidine ring so it's always able to polarize the imidazole.
Figure 8: Phe254, a surface hydrophobic residue. See text for discussion. Moving away from residues involved in the active site, one can examine where hydrophobic conserved residues fall within the protein. As Kendrew's rules say, (1) Hydrophilic residues are on the surface, (2) Hydrophobic residues are in the core, and (3) Any violation of the above rules indicates function. Following this, there is an odd occurrence of a 100% conserved hydrophobic residue on the surface of the protein away from the active site, Phe354 (Figure 8). As this is grossly energetically unfavorable, it must serve some purpose, although what purpose exactly remains unclear. If one looks at nearby nonhydrophobic conserved residues, one finds Ala39 and Asp22, both about 4-5A from the phenylalanine ring. This suggests some sort of binding site for an inhibitor or activator, because no structural stability is possible from it, and the
Page 1 and 2: Discovering critical residues in gl
Page 3 and 4: To understand possible changes in G
Page 5 and 6: Materials and Methods Multiple sequ
Page 7 and 8: Figure 1: Alignment of Arg218. From
Page 9 and 10: sequences, a convenient feature of
Page 11 and 12: Figure 4: Ile26 in FAD binding. See
Page 13: Figure 6: The Cys58-Cys63 disulfide
Page 17 and 18: Figure 10: Structural stabilization

Discovering critical residues in glutathione reductase - Gentoo

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?