Prothrombin structure: unanticipated features and opportunities

Pozzi, Nicola; Di, Enrico

doi:10.1586/14789450.2014.971763

Cited by 13 publications

(9 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…28 The site of binding on the prothrombin molecule is still under research, and it may be possible that different types of antibodies can recognize different sites of the prothrombin molecule. 29 So far, it has been established that aPS/PT and aPT represent two different types of antibodies that can be present concurrently in some cases. 30,31 Prethrombin 1 and fragment 1 and fragment 1 þ 2 have been reported as potential antigens recognized by antiprothrombin antibodies, suggesting that the dominant epitopes are likely to be located near the phospholipid-binding site of the prothrombin molecule.…”

Section: Discussionmentioning

confidence: 99%

Antiphosphatidylserine/Prothrombin Antibodies: An Update on Their Association with Clinical Manifestations of Antiphospholipid Syndrome

et al. 2020

View full text Add to dashboard Cite

Objective The aim of the study is to perform a systematic review on the recent available evidence on antiphosphatidylserine/prothrombin (aPS/PT) antibodies and their association with clinical manifestations of the antiphospholipid syndrome (APS). Methods A detailed literature search was applied a priori to Ovid MEDLINE, In-Process and Other Non-Indexed Citation 2012 to present and to abstract from EULAR and ACR/ARHP Annual Meetings (2012–2019). Results Data from 2,901 patients, 587 diseases controls and 559 healthy controls included in 15 retrieved studies was analyzed. The patient population included 1,219 patients classified as APS according to the Sidney criteria, 285 patients with isolated persistently positive antiphospholipid antibodies (aPL) and 1,397 patients with a clinical suspicion of APS. Twelve studies, including 1,888 patients, analyzed the association between aPS/PT antibodies and thrombosis. We observed a statistically significant association between aPS/PT IgG/IgM positivity and thrombotic events (mean odds ratio [OR]: 6.8 [95% CI: 3.18–16.4], p < 0.05), confirmed when analyzing aPS/PT IgG (mean OR: 6.7 [95% CI: 3.04–21.6], p < 0.05) and aPS/PT IgM (mean OR: 4.35 [95% CI: 1.54–17.77], p < 0.05) separately. Seven studies, including 1,388 patients, evaluated the association between aPS/PT antibodies and PM. When pooled together, we found a statistically significant association between any PM and aPS/PT IgG/IgM positivity (mean OR: 10.6 [95% CI: 3.54–35.38], p < 0.05), particularly aPS/PT IgG positivity (mean OR: 6.7 [95% CI: 3.04–21.6], p < 0.05). Conclusion Our results highlight the strong association between aPS/PT and the clinical manifestations of APS. With the available level of evidence, aPS/PT testing can be considered as a robust test applicable in the investigation of patients suspected for APS, also beyond the research settings.

show abstract

Section: Discussionmentioning

confidence: 99%

Antiphosphatidylserine/Prothrombin Antibodies: An Update on Their Association with Clinical Manifestations of Antiphospholipid Syndrome

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In the case of small cofactors like Na + , perturbation of S195 is sufficient to abrogate the allosteric effect. In the case of macromolecular cofactors like thrombomodulin and factor Va, the residual enhancement of catalytic activity (Figure C and Table ) is ascribed to the additional effect that these cofactors exert on the substrates protein C , and prothrombin, respectively.…”

Section: Resultsmentioning

confidence: 99%

Why Ser and Not Thr Brokers Catalysis in the Trypsin Fold

et al. 2015

Self Cite

View full text Add to dashboard Cite

Although Thr is equally represented as Ser in the human genome and is as good a nucleophile, it is never found in the active site of the large family of trypsin-like proteases that utilize the Asp/His/Ser triad. The molecular basis of the preference of Ser over Thr in the trypsin fold was investigated with X-ray structures of the thrombin mutant S195T free and bound to an irreversible active site inhibitor. In the free form, the methyl group of T195 is oriented toward the incoming substrate in a conformation seemingly incompatible with productive binding. In the bound form, the side chain of T195 reorients for efficient substrate acylation without causing steric clash within the active site. Rapid kinetics prove that this change is due to selection of an active conformation from a pre-existing ensemble of reactive and unreactive rotamers whose relative distribution determines the level of activity of the protease. Consistent with these observations, the S195T substitution is associated with a weak yet finite activity that enables identification of an unanticipated important role for S195 as the end-point of allosteric transduction in the trypsin fold. The S195T mutation abrogates the Na+-dependent enhancement of catalytic activity in thrombin, activated protein C and factor Xa, and significantly reduces the physiologically important allosteric effects of thrombomodulin on thrombin and of cofactor Va on factor Xa. The evolutionary selection of Ser over Thr in trypsin-like proteases was therefore driven by the need for high catalytic activity and efficient allosteric regulation.

show abstract

“…Sol-gel degradation in physiologic conditions gives rise to different debris and/or silica-derivate molecular components from sol-gel, which may interact with the blood, causing coagulation complications, or with the walls of the veins with which the catheter is in contact. Fibrinogen and prothrombin are liver-generated proteins which play roles in blood clotting and the inflammatory response, among other things [25,26]. Abnormal values of these parameters can be related to abnormalities in blood coagulation or inflammatory processes [26,27].…”

Section: Discussionmentioning

confidence: 99%

“…Fibrinogen and prothrombin are liver-generated proteins which play roles in blood clotting and the inflammatory response, among other things [ 25 , 26 ]. Abnormal values of these parameters can be related to abnormalities in blood coagulation or inflammatory processes [ 26 , 27 ]. According to our results, none of them showed a significant difference constant over time between the control catheter group and A50-coated catheter group ( Figure 5 B,C) despite the visible silica release from A50 sol-gel detected in serum at least during the first week ( Figure 5 D).…”

Section: Discussionmentioning

confidence: 99%

A New Antibiotic-Loaded Sol-Gel can Prevent Bacterial Intravenous Catheter-Related Infections

et al. 2020

View full text Add to dashboard Cite

The aim of this study was to evaluate the effectiveness of a moxifloxacin-loaded organic–inorganic sol-gel (A50) by locally preventing the catheter-related bloodstream infection (CRBSI) provoked by Staphylococcus epidermidis (S. epidermidis) and the effect resulting from its hydrolytic degradation on coagulation by using a rabbit in-vivo model. A50 coating can completely inhibit growth and would locally prevent CRBSI provoked by S. epidermidis. None of the coagulation blood parameters showed a significant difference constant over time between the control catheter group and the A50-coated catheter group, despite the visible silica release resulting from physiological A50 sol-gel degradation detected in serum at least during the first week. At pathological level, foreign body reaction was present in both of types of catheter, and it was characterized by the presence of macrophages and foreign body giant cell. However, this reaction was different in each group: the A50-coated catheter group showed a higher inflammation with histiocytes, which were forming granuloma-like aggregates with an amorphous crystalline material inside, accompanied by other inflammatory cells such as plasma cells, lymphocytes and mast cells. In conclusion, A50 coating a venous catheter showed excellent bactericidal anti-biofilm response since it completely inhibited S. epidermidis biofilm development and, far from showing procoagulant effects, showed slightly anticoagulant effects.

show abstract

Prothrombin structure: unanticipated features and opportunities

Cited by 13 publications

References 31 publications

Antiphosphatidylserine/Prothrombin Antibodies: An Update on Their Association with Clinical Manifestations of Antiphospholipid Syndrome

Antiphosphatidylserine/Prothrombin Antibodies: An Update on Their Association with Clinical Manifestations of Antiphospholipid Syndrome

Why Ser and Not Thr Brokers Catalysis in the Trypsin Fold

A New Antibiotic-Loaded Sol-Gel can Prevent Bacterial Intravenous Catheter-Related Infections

Contact Info

Product

Resources

About