P Hima Bindu | PubMed Health

PubMed2004

Characterization of calcium and magnesium binding domains of human 5-lipoxygenase.

Two calcium binding sites, separated by about 9.3A, present in the loops that connect the beta-sheets of N-terminal domain contain the ligating residues F14, A15, G16, D79, and D18, D19, L76, respectively. Magnesium is found to bind in regions, which are marginally different owing to the disparity in the ionic radii of Ca2+ and Mg2+. The entropy analysis on the loops of 5-lipoxygenase, implementing the wormlike chain model, explains that the N-terminal beta-barrel is well suited to accommodate calcium binding sites. The large buried side chain area of W102 (compared to W13 and W75) and comparatively smaller fraction of side chain exposed to polar atoms corroborate the calcium induced higher affinity to phosphatidylcholine (PC). However, W80 lying in close proximity of the calcium binding sites is expected to have considerable PC affinity but negligible calcium induced effect on PC binding.

Amino Acid Sequence↗

PubMed2004

Structural and conformational changes concomitant with the E1-E2 transition in H(+)K(+)-ATPase: a comparative protein modeling study.

Comparative modeling studies on conserved regions of the gastric H(+)K(+)-ATPase reveal that the E1-E2 conformational transition induces significant tertiary structural changes while conserving the secondary structure. The residues 516-530 of the cytoplasmic domain and TM10 within the transmembrane (TM) regions undergo maximum tertiary structural changes. The luminal regions exhibit comparatively lesser tertiary structural deviations. Residues 249-304 show maximum secondary structural deviation in the conformational transition. The Cys-815 and Cys-323 residues involved in inhibitor binding are found to have smaller buried side chain areas in the E1 conformation compared to E2. Retention of activity correlates well with the buried side chain area when selected amino acid residues in TM6 are mutated using modeling techniques with bulkier amino acid residues. Conformational specificity for ion binding is corroborated with the fraction of side chains exposed to polar atoms of the residues E345, D826, V340, A341, V343, and E822.

H(+)-K(+)-Exchanging ATPase↗