Heme proteins—Diversity in structural characteristics, function, and folding

Abstract

The characteristics of heme prosthetic groups and their binding sites have been analyzed in detail in a data set of nonhomologous heme proteins. Variations in the shape, volume, and chemical composition of the binding site, in the mode of heme binding and in the number and nature of heme-protein interactions are found to result in significantly different heme environments in proteins with different functions in biology. Differences are also seen in the properties of the apo states of the proteins. The apo states of proteins that bind heme permanently in their functional form show some disorder, ranging from local unfolding in the heme binding pocket to complete unfolding to give a random coil. In contrast, proteins that bind heme transiently are fully folded in their apo and holo states, presumably allowing both apo and holo forms to remain biologically active resisting aggregation or proteolysis. The principles identified here provide a framework for the design of de novo proteins that will exhibit tight heme ligand binding and for the identification of the function of structural genomic target proteins with heme ligands.

Prevalence and Gene Characteristics of Antibodies with Cofactor-induced HIV-1 Specificity

“…ing promiscuity of heme. Indeed, computational and experimental studies have revealed that heme-binding motifs on distinct proteins are characterized by a vast diversity of sequences and structures (44,45). We hypothesized that heme could interact with Abs in many alternative ways, depending on the sequence of the variable region.…”

Endoplasmic reticulum anchored heme-oxygenase 1 faces the cytosol

“…1 When released from hemoproteins, heme is degraded by heme-oxygenase (HO)1 or HO2. The subcellular location of heme protein degradation is not uniform.…”

Protoporphyrin IX: the Good, the Bad, and the Ugly

“…Its tetrapyrrole structure enables it to chelate transition metals to form metalloporphyrins, which perform a variety of biologic functions. Chelation of PPIX with iron forms heme (iron PPIX), which is a constituent of hemoproteins that play critical roles in oxygen transport, cellular oxidations and reductions, electron transport, and drug metabolism (Paoli et al, 2002;Kirton et al, 2005;Smith et al, 2010). Amounts of PPIX in cells actively synthesizing heme remain low under physiologic conditions, because the amount supplied does not exceed what is needed for heme synthesis.…”