[9] Infrared methods for study of hemoglobin reactions and structures

Dong, Aichun; Caughey, Winslow S.

doi:10.1016/0076-6879(94)32047-0

Cited by 189 publications

(215 citation statements)

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“…The frequency of an S-H stretching band increases with increasing bond strength and the intensity increases as the strength of the dipole associated with the S-H bond increases (5,30). The Cys 34 S-H stretching band at 2563 cm Ϫ1 , as induced by both NNO and NO, suggests a nonpolar environment and hydrogen bonding between the thiol and an adjacent proton acceptor such as His 39 or Tyr 84 .…”

Section: Discussionmentioning

confidence: 99%

Anesthetic-like Interactions of Nitric Oxide with Albumin and Hemeproteins

Sampath¹,

Zhao²,

Caughey³

2001

Journal of Biological Chemistry

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The mechanisms of anesthesia and the regulatory functions of nitric oxide (NO) 1 remain far from clear. Potential roles of anesthetic-protein interactions in anesthesia have become of increasing interest (1-5) as have the interactions of NO with proteins (6 -10). Volatile anesthetics occupy hydrophobic sites within protein without formation of covalent bonds with amino acid residues. In contrast, the reactions between NO and receptor sites in proteins that have been studied extensively involve covalent bond formation, as in metal nitrosyl and Snitrosothiol (-SNO) derivatives (7-10). Nitrosations (i.e. attack of protein residues by NOϩ) on exposure of proteins to NO with a suitable oxidant present are the only reactions of NO that have been discussed other than the binding of NO to metal sites. Evidence of NO occupying sites within proteins as an uncharged diatomic free radical by means of anesthetic-like noncovalent bonding has not been reported.The binding of volatile anesthetics to serum albumins and the effects of such binding on protein structure are considered in several recent reports. Specific, saturable binding of halothane and other anesthetics to bovine serum albumin and anesthetic-induced alterations in the structure or carrier function of this protein have been shown (11-16). The anesthetic nitrous oxide (NNO) was detected at sites within human serum albumin (HSA) (5). Infrared (IR) spectra of bound NNO molecules demonstrated sites of two types. The exposure of HSA to NNO enhanced absorbance in the S-H stretching region of the IR spectrum giving evidence of an NNO-induced change in protein conformation near Cys 34 (5). In 1992, NO was proposed to circulate in mammalian plasma primarily in association with serum albumin, due to formation of the S-nitrosothiol derivative (17). However, the similarities in the structure and physical properties of NNO and NO suggest the possibility that NO may also interact at some sites within albumin in the manner shown for NNO.IR evidence of NNO molecules at multiple sites within hemoglobin, myoglobin, and cytochrome c oxidase (CcO) has also been obtained (5,18). NNO neither serves as a ligand to heme iron nor reacts with thiols. The ability of NNO to alter hemeprotein structure and function was shown by shifts in the IR spectra of cysteine thiols of HbA (5) and by partial and reversible inhibitions of CcO (18). The well established ability of NO to ligate to heme iron in HbA, Mb, and CcO, and to copper B in CcO (19,20), led to the assumption of metal binding in proposed mechanisms for physiologically important reactions of NO with hemeproteins. Reactions of NO with HbA that result in S-nitrosothiol derivative formation have also received much attention (8). However, alternative mechanisms whereby NO alters hemeprotein structure and function by noncovalent anesthetic-like bonding to sites that involve neither metal nor cysteine sulfur remain unexplored.Much interest in possible physiological roles of carbon monoxide (CO), including a messenger role in the nervous syst...

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Section: Discussionmentioning

confidence: 99%

Anesthetic-like Interactions of Nitric Oxide with Albumin and Hemeproteins

Sampath¹,

Zhao²,

Caughey³

2001

Journal of Biological Chemistry

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“…Reference spectra were recorded under identical scanning conditions with only the corresponding buffer in the cell. Protein spectra were obtained according to previously established criteria and a subtraction procedure (33). The residual water vapor signals, if present, in the spectrum of protein were removed by subtracting the spectrum of gaseous water.…”

Section: Methodsmentioning

confidence: 99%

TATA box binding protein induces structure in the recombinant glucocorticoid receptor AF1 domain

Kumar

Volk

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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A number of transcription factor proteins contain domains that are fully or partially unstructured. The means by which such proteins acquire naturally folded conformations are not well understood. When they encounter their proper binding partner(s), several of these proteins adopt a folded conformation through an induced-fit mechanism. The glucocorticoid receptor (GR) is a ligand-activated transcription factor. Expressed independently as a recombinant peptide, the N-terminal transactivation domain (AF1) of the GR shows little structure and appears to exist as a collection of random coil configurations. The GR AF1 is known to interact with other transcription factors, including a critical component of the general transcription machinery proteins, the TATA box binding protein (TBP). We tested whether this interaction can lead to acquisition of structure in the GR AF1. Our results show that recombinant GR AF1 acquires a significant amount of helical content when it interacts with TBP. These structural changes were monitored by Fourier transform infrared and NMR spectroscopies, and by proteolytic digestions. Our results support a model in which TBP binding interaction with the GR AF1 induces significantly greater helical structure in the AF1 domain. This increased helical content in the GR AF1 appears to come mostly at the expense of random coil conformation. These results are in accordance with the hypothesis that an induced-fit mechanism gives structure to the GR AF1 when it encounters TBP.glucocorticoid receptor ͉ N-terminal activation function ͉ coregulatory protein ͉ protein folding T he glucocorticoid receptor (GR) is a ligand-activated transcription factor with the domain structural arrangement typical of the nuclear hormone receptors superfamily (1-4). The GR regulates transcription of target genes by binding DNA at specific hormone response elements and͞or by interacting with other transcription factors (5-8). Although the structural organization of steroid receptors into N-terminal domain (NTD), DNA binding domain (DBD), and ligand binding domain is well characterized (9-14), precisely how transcription is regulated by them is largely unknown. For all steroid receptors, this is in part due to the lack of information about their transcription activating domain AF1, located in the NTD (9, 10). The GR AF1 sequence resembles those of acidic transactivation domains of several transcription factors (15, 16). When expressed independently, the GR AF1 shows little structure and seems to exist as an ensemble of largely unstructured conformers (17, 18). The GR AF1 is known to interact with other transcription factors, and conditional folding has been suggested to be the key for these interactions (19)(20)(21)(22).It has been reported that in the presence of trifluoroethanol, the ''core'' of AF1 (AF1 c , amino acids 187-242), located toward the C-terminal end of AF1, adopts three helical segments (17). Independent experiments have shown that substitution of the ␣-helixbreaking amino acid proline for natural residues a...

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“…The assignment of different ϪSH stretching bands in the IR spectrum of human Hb to individual cysteine residues was achieved in an elegant way by comparison with the spectrum of horse Hb, which is devoid of cysteine ␤-112, and that of bovine Hb, which contains only ␤-93 cysteine (24 ). The ϪSH stretch vibrations of cysteine residues in Hb A are sensitive to the structural changes that result from the binding of ligands, such as O 2 , CO, and NO, at the heme iron (13,31 ).…”

Section: Discussionmentioning

confidence: 99%

“…Another useful IR band in the spectra of Hb is the ϪSH stretching vibration around 2550 cm Ϫ1 , which originates from the thiols of cysteine residues. Although sulfhydryl groups give rise to very weak absorption bands, they appear in a spectral region devoid of other bands and have been exploited to probe changes in amino acid sequence, oxidation state, ligand binding, pH, and other factors (13,14 ). Human Hb has six cysteine residues per tetramer; in each symmetrical half-molecule, two are in the ␤-chain (␤-93 and ␤-112) and one is in the ␣-chain (␣-104) (24 ).…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…For example, IR spectra provided insight into the binding of ligands to the heme iron and revealed protein structural changes attributable to various factors (13,14 ). The IR absorption bands of the thiol groups in the cysteine residues of Hb have also been explored (15 ), and it was found that the conformational sensitivity of the thiol IR bands can be used to study changes in the tertiary and quaternary structure of Hb induced by perturbations of pH, temperature, and effector molecules (16 ).…”

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Infrared Spectroscopic Identification of β-Thalassemia

Liu

Tsang²,

et al. 2003

Clinical Chemistry

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Background: The aim of this study was to investigate the potential of infrared (IR) spectroscopy as a fast and reagent-free adjunct tool in the diagnosis and screening of ␤-thalassemia. Methods: Blood was obtained from 56 patients with ␤-thalassemia major, 1 patient with hemoglobin H disease, and 35 age-matched controls. Hemolysates of blood samples were centrifuged to remove stroma. IR absorption spectra were recorded for duplicate films dried from 5 L of hemolysate. Differentiation between the two groups of hemoglobin spectra was by two statistical methods: an unsupervised cluster analysis and a supervised linear discriminant analysis (LDA). Results: The IR spectra revealed changes in the secondary structure of hemoglobin from ␤-thalassemia patients compared with that from controls, in particular, a decreased ␣-helix content, an increased content of parallel and antiparallel ␤-sheets, and changes in the tyrosine ring absorption band. The hemoglobin from ␤-thalassemia patients also showed an increase in the intensity of the IR bands from the cysteine ؊SH groups. The unsupervised cluster analysis, statistically separating spectra into different groups according to subtle IR spectral differences, allowed separation of control hemoglobin from ␤-thalassemia hemoglobin spectra, based mainly on differences in protein secondary structure. The supervised LDA method provided 100% classification accuracy for the training set and 98% accuracy for the validation set in partitioning control and ␤-thalassemia samples. Conclusion: IR spectroscopy holds promise in the clinical diagnosis and screening of ␤-thalassemia.

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[9] Infrared methods for study of hemoglobin reactions and structures

Cited by 189 publications

References 47 publications

Anesthetic-like Interactions of Nitric Oxide with Albumin and Hemeproteins

Anesthetic-like Interactions of Nitric Oxide with Albumin and Hemeproteins

TATA box binding protein induces structure in the recombinant glucocorticoid receptor AF1 domain

Infrared Spectroscopic Identification of β-Thalassemia

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