Allosteric modulation of monomeric proteins*

Ascenzi, Paolo; Bocedi, Alessio; Bolli, Alessandro; Fasano, Mauro; Notari, Stefania; Polticelli, Fabio

doi:10.1002/bmb.2005.494033032470

Cited by 35 publications

(29 citation statements)

References 103 publications

(111 reference statements)

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“…The inhibitory allosteric effect of ferric heme on ligand binding to Sudlow's site I may be due to stabilization of the Neutral (N) state of HSA, which occurs between pH 4.3 and 8.0 (in the absence of allosteric effectors). Conversely, ligand binding to Sudlow's site I may impair the ferric heme-HSA formation by stabilizing the Basic (B) state of HSA, occurring between pH 4.3 and 8.0 in the presence of allosteric effectors and at pH greater than 8.0 in the absence of ligands (6,10,32,39,40,48).…”

Section: Allosteric Modulation Of Drug Binding To Hsamentioning

confidence: 99%

The extraordinary ligand binding properties of human serum albumin

Fasano

Curry

Terreno

et al. 2005

IUBMB Life (International Union of Biochemistry and Molecular B

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962

795

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SummaryHuman serum albumin (HSA), the most prominent protein in plasma, binds different classes of ligands at multiple sites. HSA provides a depot for many compounds, affects pharmacokinetics of many drugs, holds some ligands in a strained orientation providing their metabolic modification, renders potential toxins harmless transporting them to disposal sites, accounts for most of the antioxidant capacity of human serum, and acts as a NO-carrier. The globular domain structural organization of monomeric HSA is at the root of its allosteric properties which are reminiscent of those of multimeric proteins. Here, structural, functional, biotechnological, and biomedical aspects of ligand binding to HSA are summarized. IUBMB Life, 57: 787 -796, 2005

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Section: Allosteric Modulation Of Drug Binding To Hsamentioning

confidence: 99%

The extraordinary ligand binding properties of human serum albumin

Fasano

Curry

Terreno

et al. 2005

IUBMB Life (International Union of Biochemistry and Molecular B

Self Cite

962

795

View full text Add to dashboard Cite

show abstract

“…The role of transient heme binding to HDL and LDL is unclear and requires investigations. SA, the most prominent protein in plasma, is best known for its extraordinarily broad ligand binding spectrum (13,21,61,62). The three-dimensional structure of SA appears to be formed by three homologous domains, each of them being made up by two separate subdomains (named A and B) connected by a random coil.…”

Section: Scavenging Of the Toxic Plasma Hemementioning

confidence: 99%

Hemoglobin and heme scavenging

Ascenzi

Bocedi

Visca

et al. 2005

IUBMB Life (International Union of Biochemistry and Molecular B

Self Cite

234

221

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Release of hemoglobin into plasma is a physiological phenomenon associated with intravascular hemolysis. In plasma, stable haptoglobin‐hemoglobin complexes are formed and these are subsequently delivered to the reticulo‐endothelial system by CD163 receptor‐mediated endocytosis. Heme arising from the degradation of hemoglobin, myoglobin, and of enzymes with heme prosthetic groups could be delivered in plasma. Albumin, haptoglobin, hemopexin, and high and low density lipoproteins cooperate to trap the plasma heme, thereby ensuring its complete clearance. Then hemopexin releases the heme into hepatic parenchymal cells only after internalization of the hemopexin‐heme complex by CD91 receptor‐mediated endocytosis. Moreover, α1‐microglobulin contributes to heme degradation by a still unknown mechanism, with the concomitant formation of heterogeneous yellow‐brown kynurenine‐derived chromophores which are very tightly bound to amino acid residues close to the rim of the lipocalin pocket. During hemoglobin synthesis, the erythroid α‐chain hemoglobin‐stabilizing protein specifically binds free α‐hemoglobin subunits limiting the free protein toxicity. Although highly toxic because capable of catalyzing free radical formation, heme is also a major and readily available source of iron for pathogenic organisms. Gram‐negative bacteria pick up the heme‐bound iron through the secretion of a hemophore that takes up either free heme or heme bound to heme‐proteins and transports it to a specific receptor, which, in turn, releases the heme and hence iron into the bacterium. Here, hemoglobin and heme trapping mechanisms are summarized. IUBMB Life, 57: 749‐759, 2005

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“…[8][9][10][11][12][13] Both allosteric regulation in monomeric proteins and purely entropy-driven allostery have been described. [14][15][16] The role of protein dynamics in determining function is becoming more recognized, contributing to the increase in our understanding of protein function and regulation. [8][9][10][11][12][13] The enzyme 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first reaction in the shikimate pathway, the pathway responsible for the biosynthesis of the aromatic amino acids Trp, Phe, and Tyr.…”

Section: Introductionmentioning

confidence: 99%

Three Sites and You Are Out: Ternary Synergistic Allostery Controls Aromatic Amino Acid Biosynthesis in Mycobacterium tuberculosis

Blackmore

Reichau

Jiao

et al. 2013

Journal of Molecular Biology

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Abstract3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first step in the shikimate pathway, the pathway responsible for the biosynthesis of the aromatic amino acids Trp, Phe, and Tyr. Unlike many other organisms that produce up to three isozymes, each feedback-regulated by one of the aromatic amino acid pathway end products, Mycobacterium tuberculosis expresses a single DAH7PS enzyme that can be controlled by combinations of aromatic amino acids. This study shows that the synergistic inhibition of this enzyme by a combination of Trp and Phe can be significantly augmented by the addition of Tyr. We used X-ray crystallography, mutagenesis, and isothermal titration calorimetry studies to show that DAH7PS from M. tuberculosis possesses a Tyr-selective site in addition to the Trp and Phe sites, revealing an unusual and highly sophisticated network of three synergistic allosteric sites on one enzyme. This ternary inhibitory response, by a combination of all three aromatic amino acids, allows a tunable response of the protein to changing metabolic demands.

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Allosteric modulation of monomeric proteins*

Cited by 35 publications

References 103 publications

The extraordinary ligand binding properties of human serum albumin

The extraordinary ligand binding properties of human serum albumin

Hemoglobin and heme scavenging

Three Sites and You Are Out: Ternary Synergistic Allostery Controls Aromatic Amino Acid Biosynthesis in Mycobacterium tuberculosis

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