Where is the oxygen binding site of cytochrome c oxidase? Transmembrane helices of subunits I and II

The Transmembrane Helices of Beef Heart Cytochrome Oxidase

“…We used our scale to predict the transmembrane helices in the L and M subunits of the photosynthetic reaction center of Rhodopsomonas viridis to assure ourselves that we were not grossly overor underpredicting transmembrane helical segments by our method. We found that we had predicted correctly all ten of the transmembrane helices in these two subunits and that only two residues in the L subunit and only one residue in the M subunit were incorrectly predicted to be a transmembrane helical residue as part of the 19-residue stretch with the highest hydrophobicity (3,5). These results are shown in the footnote to Table I.…”

“…Finally, there is the problem of what the length of a transmembrane helix actually is. We find that 18or 19-residue segments are more useful in locating the probable transmembrane stretches in a membrane protein than longer segments if hydrophobicity profiles are used because charged residues may be present particularly in the lipid head region (3,6,7,15). The transmembrane helices observed in the crystal structure of the photosyn-thetic reaction center of Rhodopseudomonas viridis range in length from 24-30 residues and, therefore, can not be predicted in their entirety from the hydrophobicity profile of a 19-residue moving window using the hydropathy scale of Kyte and Doolittle (5,19) or Table I (3).…”

“…von Heijne (15) points out that a "simple" integral membrane protein with a single transmembrane segment will be -21 residues long to get across the nonpolar part of the membrane (>30 A long). For 24 transmembrane helices in beef heart COX with -20-21 $1.00 PROPERTIES The estimated hydrophobic free energy gain (H') when a side chain in a protein in random coil conformation is taken out of contact with aqueous solution is based on 25 cal/A2 of accessible surface area (ASA) gain with appropriate corrections for hydrogen-bond loss (H-bond) and electrostatic charge neutralization (Charge) contributions (3,4). The assigned hydrophobicity value H in the last column has the opposite sign from the estimated free energy change (AGH, kcal/residue) that is shown.…”

“…There is room in the cytochrome oxidase molecule for this many transmembrane helices (17,18). (Some estimates of the number of transmembrane helical segments in the largest subunits, subunits I and III, differ from ours [3,5,[18][19][20][21][22]). We predict the same transmembrane helices in all species for which we had sequence information using the scale shown in Table I.…”

Conformational analysis of HIV-1 protease inhibitors: 2. Thioproline P1? Residue in the potent inhibitor KNI-272

“…following proline a ␥-turn are known in cyclic peptides. 22 However, the formation of a ␤-turn involving proline is much more commonly found 23,24 and is generally through to be energetically preferable. 25 This suggests that if there are opportunities for the norstatine᎐thioproline portion of KNI-272 to form intermolecular hydrogen bonds to HIV-PR, those hydrogen bonds will probably be preferred.…”