Zn2+ Mediates High Affinity Binding of Heparin to the αC Domain of Fibrinogen

Fredenburgh, James C.; Leslie, Beverly A.; Stafford, Alan R.; Lim, Teresa; Chan, Howard H.W.; Weitz, Jeffrey I.

doi:10.1074/jbc.m113.469916

Cited by 26 publications

(42 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another Zn 2+ -binding region has been identified in the αC-domain and also involves histidine residues (His-α544 and His-α545). 75 Binding of Zn 2+ to this region is thought to induce a change in the conformation of the protein. 75 Based on several studies, Zn 2+ binding to fibrinogen has an average K d of ∼1–18 μM, but the individual contributions of the two groups of sites are unknown.…”

Section: Impact Of Zn 2+ On Protein–gag Interactiomentioning

confidence: 99%

“… 75 Binding of Zn 2+ to this region is thought to induce a change in the conformation of the protein. 75 Based on several studies, Zn 2+ binding to fibrinogen has an average K d of ∼1–18 μM, but the individual contributions of the two groups of sites are unknown. 27 , 36 , 75 …”

Section: Impact Of Zn 2+ On Protein–gag Interactiomentioning

confidence: 99%

“… 76 A second heparin-binding mode occurs when Zn 2+ binds to the αC domains of fibrinogen. 75 Binding of Zn 2+ is thought to induce a change in the conformation of the protein promoting heparin-binding to the nearby E domain. 75 In presence of 12.5 μM Zn 2+ , the average K d for heparin binding to fibrinogen is 60 nM.…”

Section: Impact Of Zn 2+ On Protein–gag Interactiomentioning

confidence: 99%

See 2 more Smart Citations

Influence of zinc on glycosaminoglycan neutralisation during coagulation

2018

View full text Add to dashboard Cite

show abstract

Section: Impact Of Zn 2+ On Protein–gag Interactiomentioning

confidence: 99%

Section: Impact Of Zn 2+ On Protein–gag Interactiomentioning

confidence: 99%

Section: Impact Of Zn 2+ On Protein–gag Interactiomentioning

confidence: 99%

See 1 more Smart Citation

Influence of zinc on glycosaminoglycan neutralisation during coagulation

2018

View full text Add to dashboard Cite

show abstract

“…Underlying coagulopathy or thrombocytopenia should be corrected by transfusion of plasma, cryoprecipitate, or platelets as clinically indicated. After surgery, during the acute phase response, optimal heparin management is challenging since heparin binds some acute phase reactants, such as vitronectin, 14 fibrinogen, 15 plasminogen activator inhibitor 1 16 and von Willebrand factor (VWF). 17 Heparin therapy should frequently be monitored, and the dose should be adjusted at the target anti-Xa of 0.2 to 0.4 units/mL as soon as clinically tolerated.…”

Section: Hemostasis Management Acute Phasementioning

confidence: 99%

Management of Hemostasis for Pediatric Patients on Ventricular-Assist Devices

Adachi

Kostousov

Hensch

et al. 2017

Semin Thromb Hemost

View full text Add to dashboard Cite

Ventricular-assist devices (VADs) have seen increased utilization in the pediatric population. Formerly, this therapeutic modality was limited to only the pulsatile VAD, EXCOR (Berlin Heart GmbH). However, the continuous flow VAD devices, HeartMate II (Abbott Inc.) and HeartWare (Medtronic Inc.), are now increasingly used in this population. Postoperatively, VAD patients are acutely anticoagulated using unfractionated heparin, often beginning 24 to 48 hours after VAD placement. Once the patient is stabilized and ready to transition to a lower acuity or outpatient setting, low-molecular-weight heparin or warfarin therapy may be instituted. Also, because of the risk for thrombotic and thromboembolic complications, antiplatelet strategies are employed using medications such as aspirin, clopidogrel, or dipyridamole. Platelet-rich plasma or whole blood platelet aggregation studies, platelet function analyzer-100 (Siemens), VerifyNow (Accriva Diagnostics), or thromboelastography platelet mapping (Haemonetics) may be used to help monitor antiplatelet effects, though the interpretation of the strength of the antiplatelet effect remains difficult. Care must be taken to monitor the hematologic complications of VAD, including acquired von Willebrand syndrome, which increases the risk for bleeding, and intravascular hemolysis, which increases the risk of thrombosis. Appropriate device placement and anticoagulation management are imperative to help avoid neurological dysfunction and ischemic stroke, the most devastating potential complications of VAD therapy. As our experience grows, we continue to gain an increased understanding of the management of anticoagulation, need for antiplatelet medication, and appropriate monitoring for these critical patients.

show abstract

“…Interestingly, a recent study by Fredenburgh et al has revealed that fibrinogen, like HRG, also binds heparin with high affinity in a Zn 2+ -dependent manner [74]. Fibrinogen is a glycoprotein present in plasma at a concentration of around 6-12 μM [71,75].…”

Section: Ffa-mediated Alterations In Plasma Zinc Speciation: Implicatmentioning

confidence: 99%

Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease

Blindauer

Khazaipoul²,

Yu³

et al. 2016

CTMC

View full text Add to dashboard Cite

(2016) Fatty acid-mediated inhibition of metal binding to the multi-metal site on serum albumin : implications for cardiovascular disease. Current Trends in Medicinal Chemistry, 16. Permanent WRAP URL:http://wrap.warwick.ac.uk/78963 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-for-profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way.Publisher's statement: © Bentham Science Publishers. http://dx.doi.org/10.2174/1568026616666160216155927 A note on versions:The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher's version. Please see the 'permanent WRAP URL' above for details on accessing the published version and note that access may require a subscription. Abstract: Human serum albumin (HSA) is the major protein in blood plasma and is responsible for circulatory transport of a range of small molecules including fatty acids, metal ions and drugs. We previously identified the major plasma Zn 2+ transport site on HSA and revealed that fatty-acid binding (at a distinct site called the FA2 site) and Zn 2+ binding are interdependent via an allosteric mechanism. Since binding affinities of long-chain fatty acids exceed those of plasma Zn 2+ , this means that under certain circumstances the binding of fatty acid molecules to HSA is likely to diminish HSA Zn 2+ -binding, and hence affects the control of circulatory and cellular Zn 2+ dynamics. This relationship between circulatory fatty acid and Zn 2+ dynamics is likely to have important physiological and pathological implications, especially since it has been recognised that Zn 2+ acts as a signalling agent in many cell types. Fatty acid levels in the blood are dynamic, but most importantly, chronic elevation of plasma fatty acid levels is associated with some metabolic disorders and disease states -including myocardial infarction and other cardiovascular diseases. In this article, we briefly review the metalbinding properties of albumin and highlight the importance of their interplay with fatty acid binding. We also consider the impact of this dynamic link upon levels and speciation of plasma Zn 2+ , its effect upon cellular Zn 2+ homeostasis and its relevance to cardiovascular and circulatory processes in health and disease.

show abstract

Zn2+ Mediates High Affinity Binding of Heparin to the αC Domain of Fibrinogen

Cited by 26 publications

References 50 publications

Influence of zinc on glycosaminoglycan neutralisation during coagulation

Influence of zinc on glycosaminoglycan neutralisation during coagulation

Management of Hemostasis for Pediatric Patients on Ventricular-Assist Devices

Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease

Contact Info

Product

Resources

About