Heme‐hemopexin: A ‘Chronosteric’ heme‐protein

Ascenzi, Paolo; Fasano, Mauro

doi:10.1080/15216540701689666

Cited by 20 publications

(21 citation statements)

References 34 publications

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“…Finally, the possibility that partially unfolded Hb derivatives may display transient ligand‐binding properties different from those of the native globin and of the unfolded protein may represent a case of “chronosteric effects” (45–47). Remarkably, the Hb reactivity toward CO increases transiently at low pH (<4), preceding the irreversible protein denaturation.…”

Section: Discussionmentioning

confidence: 99%

Reactivity of the human hemoglobin “Dark side”

2013

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Ligand binding to the heme distal side is a paradigm of biochemistry. However, X-ray crystallographic studies highlighted the possibility that O(2) and NO(2) (-) may bind to the proximal heme side of ferrous human hemoglobin (Hb) α-chains complexed with the α-hemoglobin stabilizing protein and to ferric human hemoglobin β-chains, respectively. Strikingly, the role generally played by the proximal HisF8 residue is played by the distal HisE7 side chain forming the trans axial ligand of the heme-Fe atom. This: i) brings to light that Hb may utilize both heme distal and proximal sides for ligand discrimination, ii) draws attention to the nonequivalence of α- and β-chains, and iii) highlights the possibility that partially unfolded Hb derivatives may display transient ligand-binding properties different from those of the native globin.

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Section: Discussionmentioning

confidence: 99%

Reactivity of the human hemoglobin “Dark side”

2013

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“…After delivering the heme intracellularly, HPX is released intact into the bloodstream and the heme is degraded (see refs. ).…”

Section: Human Serum Albumin: a “Chronosteric Protein”mentioning

confidence: 97%

“…Of note, HPX, whose plasma concentration (~1.5 μM) is about two orders of magnitude lower than that of SA (~700 μM) in humans, undergoes heme‐Fe saturation under pathological conditions and SA acts as the main heme‐Fe plasma depot (see refs. ).…”

Section: Human Serum Albumin: a “Chronosteric Protein”mentioning

confidence: 97%

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Functional role of transient conformations: Rediscovering “chronosteric effects” thirty years later

Ascenzi

Gianni

2013

IUBMB Life

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Proteins are dynamic entities that exert, in some cases, their functions via complex pathways, involving active transient species. This phenomenon was highlighted for the first time in 1983 by Antonini et al. (J. Biol. Chem. 258,[4676][4677][4678], who demonstrated that at least one intermediate occurring in the formation of the bovine b-trypsin-Kunitz inhibitor complex displayed catalytic properties different from those of the active enzyme and of the inactive enzyme-inhibitor adduct. Since it was impossible to explain this phenomenon in terms of static three-dimensional structures, the term "chronosteric effects" was coined to capture the observation that transient species are relevant to protein function(s). Here, some recent results on the folding and function of proteins are reported on the light of chronosteric effects.

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“…These biological consequences of heme binding by circulating hemopexin are well documented and have been reviewed extensively. [4][5][6][7] Physicalchemical understanding of hemopexin and the complex it forms with heme were advanced significantly by crystallographic determination of the three-dimensional structure of the rabbit hemopexin-heme complex by Baker and coworkers. 1,8 This structure established that hemopexin is comprised of homologous Nand C-terminal domains having similar 4-bladed bpropeller folding motifs that are joined by a flexible hinge sequence.…”

Section: Hemopexinmentioning

confidence: 99%

An alternative view of the proposed alternative activities of hemopexin

2011

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Hemopexin is a plasma protein that plays a well-established biological role in sequestering heme that is released into the plasma from hemoglobin and myoglobin as the result of intravascular or extravascular hemolysis as well as from skeletal muscle trauma or neuromuscular disease. In recent years, a variety of additional biological activities have been attributed to hemopexin, for example, hyaluronidase activity, serine protease activity, proinflammatory and anti-inflammatory activity as well as suppression of lymphocyte necrosis, inhibition of cellular adhesion, and binding of divalent metal ions. This review examines the challenges involved in the purification of hemopexin from plasma and in the recombinant expression of hemopexin and evaluates the questions that these challenges and the characteristics of hemopexin raise concerning the validity of many of the new activities proposed for this protein. As well, an homology model of the three-dimensional structure of human hemopexin is used to reveal that the protein lacks the catalytic triad that is characteristic of many serine proteases but that hemopexin possesses two highly exposed Arg-Gly-Glu sequences that may promote interaction with cell surfaces.

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Heme‐hemopexin: A ‘Chronosteric’ heme‐protein

Cited by 20 publications

References 34 publications

Reactivity of the human hemoglobin “Dark side”

Reactivity of the human hemoglobin “Dark side”

Functional role of transient conformations: Rediscovering “chronosteric effects” thirty years later

An alternative view of the proposed alternative activities of hemopexin

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