Biomaterial Database

Structure of the lysine-fibrin binding subsite of human plasminogen kringle 4. 1990

A M Mulichak, and A Tulinsky

Department of Chemistry, Michigan State University, East Lansing 48824.

Human plasminogen kringle 4, which crystallizes in the orthorhombic system a = 32.15(2), b = 49.01(2), c = 49.04(3) A, space group P2(1)2(1)2(1), four molecules per unit cell, protein volume fraction 0.62, has been determined at 1.9 A resolution. The structure was solved by rotation-translation methods using the structure of bovine prothrombin kringle 1 as a model and it has been refined at 1.9 A resolution to an R-value of 0.142. The root mean square (rms) deviation between the main-chain atoms of the two kringles is about 0.5 A while that between 31 conserved side chains is a surprisingly large 1.2 A. The structure of the lysine binding subsite of fibrin binding of kringle 4 is approximated well by prothrombin kringle 1 but with some notable exceptions. The latter transform the site from a non-binding kringle to one which recognizes lysine and other omega-amino-carboxylic acids. The binding site of the observed kringle 4 structure is also compared with one that was modelled from the structure of kringle 1 of prothrombin fragment 1 and NMR observations. Arginine residues of the binding site of a neighbouring molecule make ion pairs with aspartic acid residues in the binding site of another molecule in the kringle 4 structure.

UI	MeSH Term	Description	Entries
D008239	Lysine	An essential amino acid. It is often added to animal feed.	Enisyl,L-Lysine,Lysine Acetate,Lysine Hydrochloride,Acetate, Lysine,L Lysine
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010958	Plasminogen	Precursor of plasmin (FIBRINOLYSIN). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent.	Profibrinolysin,Glu-Plasminogen,Glutamic Acid 1-Plasminogen,Glutamyl Plasminogen,1-Plasminogen, Glutamic Acid,Glu Plasminogen,Glutamic Acid 1 Plasminogen,Plasminogen, Glutamyl
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D011487	Protein Conformation	The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).	Conformation, Protein,Conformations, Protein,Protein Conformations
D005337	Fibrin	A protein derived from FIBRINOGEN in the presence of THROMBIN, which forms part of the blood clot.	Antithrombin I
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein