Three-dimensional structure of diferric bovine lactoferrin at 2.8 Å resolution

Moore, Stanley A.; Anderson, Bill; Groom, Colin R.; Haridas, M.; Baker, Edward N.

doi:10.1006/jmbi.1997.1386

Cited by 366 publications

(275 citation statements)

References 58 publications

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“…Therefore, iron release from the C-site of ovotransferrin occurs by a mechanism similar to that for serum-transferrin with, however, lower rates and the involvement of an additional proton transfer. This additional proton transfer can be due to the discrepancies in the interdomain H-bonds which exist in each of the iron-binding clefts of the two proteins [29]. These H-bonds can break upon protonation of the amino acids involved rendering the metal more accessible to the outside medium [9].…”

Section: Discussionmentioning

confidence: 99%

Transferrins, the mechanism of iron release by ovotransferrin

Abdallah

Chahine

1999

European Journal of Biochemistry

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Iron release from ovotransferrin in acidic media (3 , pH , 6) occurs in at least six kinetic steps. The first is a very fast (# 5 ms) decarbonation of the iron-loaded protein. Iron release from both sites of the protein is controlled by what appear to be slow proton transfers. The N-site loses its iron first in two steps, the first occurring in the tenth of a second range with second order rate constant k 1 = (2.30^0.10) Â 10 4 m 21´s21 , first order rate constant k 21 = (1.40^0.10) s 21 and equilibrium constant K 1a = (60^6) mm. The second step occurs in the second range with a second order rate constant k 2 = (5.2^0.15) Â 10 3 m 21´s21 , first order rate constant k 22 = (0.2^0.02) s 21 and equilibrium constant K 2a = (39^5) mm. Iron is afterward lost from the C-site of the protein by two different pathways, one in the presence of a strong Fe(III) ligand such as citrate and the other in the presence of weak ligands such as formate or acetate. The first step, common to both paths, is a slow proton uptake which occurs in the tens of second range with a second order rate constant k 3 = (1.22^0.03) Â 10 3 m 21´s21 and equilibrium constant K 3a = (1.0^0.1) mm. In the presence of citrate, this step is followed by formation of an intermediate complex with monoferric ovotransferrin; stability constant K LC = (0.435^0.015) mm. This last step is rate-controlled by slow proton gain which occurs in the hundred second range with a second order rate constant k 4 = (1.05^0.05) Â 10 4 m 21´s21 , first order rate constant k 24 = (1.0^0.1) Â 10 22 s 21 and equilibrium constant K 4a = (0.95^0.15) mm. In the presence of a weak iron(III) ligand such as acetate or formate, formation of an intermediate complex is not detected and iron release is controlled by two final slow proton uptakes. The first occurs in the hundred to thousand second range, second order rate constant k 5 = (6.90^0.30) Â 10 6 m 21´s21 . The last step occurs in the thousand second range. Iron release by ovotransferrin is similar but not identical to that of serum-transferrin. It is slower and occurs at lower pH values. However, as seen for serum-transferrin, it seems to involve the protonation of the amino acid sidechains involved in iron co-ordination and perhaps those implicated in interdomain H-bonds. The observed proton transfers are, then, probably controlled by the change in conformation of the binding lobes from closed when iron-loaded to open in the apo-form.Keywords: transferrin; ovotransferrin; iron metabolism; stopped-flow.Transferrins constitute the most important iron regulation system in vertebrates and some invertebrates, such as worms and insects [1]. Soluble transferrins, such as serum-transferrin, lactoferrin and ovotransferrin, are glycoproteins consisting of a single chain of about 700 amino acids and 80 kDa. These proteins have very similar 3D structures and are all bilobal. Each lobe contains an iron complexation cleft, in which the metal is co-ordinated to the side-chains of four amino acid ligands and a synergistic carbonate or bicarbonate...

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Section: Discussionmentioning

confidence: 99%

Transferrins, the mechanism of iron release by ovotransferrin

Abdallah

Chahine

1999

European Journal of Biochemistry

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“…Lactoferrin is a globular glycoprotein with a molecular weight of about 80 kDa, which shows high affinity for iron (Metz-Boutigue et al 1984). Although the overall structure of lactoferrin is very similar to that of transferrin, they differ in their relative affinities for Fe and the propensity for release of Fe (Moore et al 1997). The capability of lactoferrin to bind iron is two times higher than that of transferrin (Adlerova et al 2008).…”

Section: Lactoferrinmentioning

confidence: 99%

Acute phase proteins and their use in the diagnosis of diseases in ruminants: a review

Tóthová¹,

Nagy²,

Kováč³

2014

Vet. Med. - Czech

152

159

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ABSTRACT:The acute phase response is a complex systemic early-defence system of reactions activated by trauma, infection, tissue damage, inflammation, stress or neoplasia. One of the most important elements of this response is the increased hepatic synthesis of some plasma proteins, collectively known as acute phase proteins. The discovery of these new biomarkers has allowed the clinical monitoring of different diseases; therefore, their clinical application has been studied widely in human medicine in order to improve the diagnosis, evaluation, treatment, prognosis and therapeutics of many diseases. Although a wide range of studies have been carried out to determine the usefulness of acute phase proteins in several diseases also in animals, they are still relatively under-utilised in veterinary medicine, predominantly in farm animals. The acute phase response and clinical application of acute phase proteins in ruminants are reviewed in this article, including their diagnostic use in clinical practice and application in the monitoring of treatment, which is one of the most promising practical uses of these proteins.

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“…The ability to interact with anionic heparan sulphate is maybe not that surprising, when evaluating the three dimensional structural composition of lactoferrin, demonstrating a rather striking cationic patch on the N-terminal lobe of the molecule [84] (Figure 1). Similarly, other highly cationic peptides have also been demonstrated to effectively interfere with herpes simplex virus attachment and entry [80,85].…”

Section: Protein Composition Of Milk and Their Antiviral Activitymentioning

confidence: 97%