The importance of the hydrophobic components of the binding energies in the interaction of ω‐amino acid ligands with isolated kringle polypeptide domains of human plasminogen

Menhart, Nick

doi:10.1111/j.1399-3011.1995.tb01601.x

Cited by 12 publications

(7 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specific structural domains named lysine binding sites (LBS) are present in these kringle domains and provide binding sites for lysine residues of PLG receptors [6]. KR 1 and KR 4 possess the highest binding affinity for lysine-type ligands [53–56], while KR 2 exhibits the lowest affinity [57].…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of a Trichinella spiralis enolase and its interaction with the host’s plasminogen

Jiang

Zao

Yan

et al. 2019

Vet Res

View full text Add to dashboard Cite

The binding and activation of host plasminogen (PLG) by worm surface enolases has been verified to participate in parasite invasion, but the role of this processes during Trichinella spiralis infection has not been clarified. Therefore, the expression and immunolocalization of a T. spiralis enolase (TsENO) and its binding activity with PLG were evaluated in this study. Based on the three-dimensional (3D) molecular model of TsENO, the protein interaction between TsENO and human PLG was analysed by the ZDOCK server. The interacting residues were identified after analysis of the protein–protein interface by bioinformatics techniques. The key interacting residues were confirmed by a series of experiments. The qPCR analysis results demonstrated that Ts-eno was transcribed throughout the whole life cycle of T. spiralis. The immunofluorescence assay (IFA) results confirmed that TsENO was distributed on the T. spiralis surface. The binding assays showed that recombinant TsENO (rTsENO) and native TsENO were able to bind PLG. Four lysine residues (90, 289, 291 and 300) of TsENO were considered to be active residues for PLG interaction. The quadruple mutant (Lys90Ala + Lys289Ala + Lys291Ala + Lys300Ala) TsENO, in which the key lysine residues were substituted with alanine (Ala) residues, exhibited a reduction in PLG binding of nearly 50% (45.37%). These results revealed that TsENO has strong binding activity with human PLG. The four lysine residues (90, 289, 291 and 300) of TsENO play an important role in PLG binding and could accelerate PLG activation and invasion of the host’s intestinal wall by T. spiralis.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular characterization of a Trichinella spiralis enolase and its interaction with the host’s plasminogen

Jiang

Zao

Yan

et al. 2019

Vet Res

View full text Add to dashboard Cite

show abstract

“…For example, the K1 domain contains anionic and cationic centers made up of two Asp and two Arg residues, respectively, and also a hydrophobic groove that is lined with three Tyr residues . The LBSs facilitate binding of small and large molecules, such as Lys‐like ligands, inorganic chloride, fibrin(ogen), bacterial proteins, mammalian cell surfaces, and the main physiological inhibitor α 2 ‐antiplasmin . Interestingly, despite similarity among the five LBSs, structural differences do exist among them leading to differential recognition of a ligand by the five domains.…”

Section: The Plasminogen‐plasmin Systemmentioning

confidence: 99%

Recent Advances on Plasmin Inhibitors for the Treatment of Fibrinolysis‐Related Disorders

Al‐Horani

Desai

2014

Medicinal Research Reviews

101

View full text Add to dashboard Cite

Growing evidence suggests that plasmin is involved in a number of physiological processes in addition to its key role in fibrin cleavage. Plasmin inhibition is critical in preventing adverse consequences arising from plasmin overactivity, e.g., blood loss that may follow cardiac surgery. Aprotinin was widely used as an antifibrinolytic drug before its discontinuation in 2008. Tranexamic acid and ε-aminocaproic acid, two small molecule plasmin inhibitors, are currently used in the clinic. Several molecules have been designed utilizing covalent, but reversible, chemistry relying on reactive cyclohexanones, nitrile warheads, and reactive aldehyde peptidomimetics. Other major classes of plasmin inhibitors include the cyclic peptidomimetics and polypeptides of the Kunitz and Kazal-type. Allosteric inhibitors of plasmin have also been designed including small molecule lysine analogs that bind to plasmin's kringle domain(s) and sulfated glycosaminoglycan mimetics that bind to plasmin's catalytic domain. Plasmin inhibitors have also been explored for resolving other disease states including cell metastasis, cell proliferation, angiogenesis, and embryo implantation. This review highlights functional and structural aspects of plasmin inhibitors with the goal of advancing their design.

show abstract

“…Almost all kringle modules bind to lysine or lysine-like ligands except K3. K1 and K4 exhibit the strongest ligand affinities [30–33] while K2 possesses the weakest affinity [34]. K2 shows strong affinity to a endopolypeptide (VEK-30) derived from Streptococcal Plg receptor M protein (PAM) [35].…”

Section: Key Players In the Plasminogen Systemmentioning

confidence: 99%

Bacterial Plasminogen Receptors Utilize Host Plasminogen System for Effective Invasion and Dissemination

Bhattacharya

Ploplis

Castellino

2012

Journal of Biomedicine and Biotechnology

Self Cite

116

118

View full text Add to dashboard Cite

In order for invasive pathogens to migrate beyond the site of infection, host physiological barriers such as the extracellular matrix, the basement membrane, and encapsulating fibrin network must be degraded. To circumvent these impediments, proteolytic enzymes facilitate the dissemination of the microorganism. Recruitment of host proteases to the bacterial surface represents a particularly effective mechanism for enhancing invasiveness. Plasmin is a broad spectrum serine protease that degrades fibrin, extracellular matrices, and connective tissue. A large number of pathogens express plasminogen receptors which immobilize plasmin(ogen) on the bacterial surface. Surface-bound plasminogen is then activated by plasminogen activators to plasmin through limited proteolysis thus triggering the development of a proteolytic surface on the bacteria and eventually assisting the spread of bacteria. The host hemostatic system plays an important role in systemic infection. The interplay between hemostatic processes such as coagulation and fibrinolysis and the inflammatory response constitutes essential components of host defense and bacterial invasion. The goal of this paper is to highlight mechanisms whereby pathogenic bacteria, by engaging surface receptors, utilize and exploit the host plasminogen and fibrinolytic system for the successful dissemination within the host.

show abstract

The importance of the hydrophobic components of the binding energies in the interaction of ω‐amino acid ligands with isolated kringle polypeptide domains of human plasminogen

Cited by 12 publications

References 40 publications

Molecular characterization of a Trichinella spiralis enolase and its interaction with the host’s plasminogen

Molecular characterization of a Trichinella spiralis enolase and its interaction with the host’s plasminogen

Recent Advances on Plasmin Inhibitors for the Treatment of Fibrinolysis‐Related Disorders

Bacterial Plasminogen Receptors Utilize Host Plasminogen System for Effective Invasion and Dissemination

Contact Info

Product

Resources

About