Amino acid residues of the kringle-4 and kringle-5 domains of human plasminogen that stabilize their interactions with omega-amino acid ligands
Abstract
Regions of the human plasminogen (Pg) cDNA containing its kringle 4 (K4) and K5 domains have been expressed in Escherichia coli, and binding constants of omega-amino acid ligands for recombinant (r)-[K4Pg] and r-[K5Pg] have been obtained. In each case, the results showed that of a series of aliphatic alpha, omega-amino acid analogues, 6-aminohexanoic acid showed maximal affinity for these modules, and all ligands interacted more strongly with r-[K4Pg] than with r-[K5Pg]. Site-directed mutagenesis investigations demonstrated that the major amino acid side chain contributors to ligand binding were similar for each of these kringles. Ligand binding was stabilized by charged groups at Asp56 of r-[K4Pg] and Asp57 of r-[K5Pg] as well as by Arg69 of both r-[K4Pg] and r-[K5Pg]. Some hydrophobic amino acids that contributed significantly to the binding strength of the ligands were identified. These were provided by homologous residues in each of the domains, viz. Trp60 and Trp70 of r-[K4Pg] and Trp62 and Tyr72 of r-[K5Pg]. Tyr74 of r-[K5Pg] also substantially contributed to its ligand binding energy.
Read the paper
Related studies
- eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses
- Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer
- OptiType: precision HLA typing from next-generation sequencing data
- Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications
- Saccharomyces cerevisiae cells have three Omega class glutathione S-transferases acting as 1-Cys thiol transferases
- Hemolysis at low blood flow rates: in-vitro and in-silico evaluation of a centrifugal blood pump
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.