Biomaterial Database

The refined structure of the epsilon-aminocaproic acid complex of human plasminogen kringle 4. 1991

T P Wu, and K Padmanabhan, and A Tulinsky, and A M Mulichak

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

The crystallographic structure of the plasminogen kringle 4-epsilon-aminocaproic acid (ACA) complex (K4-ACA) has been solved by molecular replacement rotation-translation methods utilizing the refined apo-K4 structure as a search model (Mulichak et al., 1991), and it has been refined to an R value of 0.148 at 2.25-A resolution. The K4-ACA structure consists of two interkringle residues, the kringle along with the ACA ligand, and 106 water molecules. The lysine-binding site has been confirmed to be a relatively open and shallow depression, lined by aromatic rings of Trp62, Phe64, and Trp72, which provide a highly nonpolar environment between doubly charged anionic and cationic centers formed by Asp55/Asp57 and Lys35/Arg71. A zwitterionic ACA ligand molecule is held by hydrogen-bonded ion pair interactions and van der Waals contacts between the charged centers. The lysine-binding site of apo-K4 and K4-ACA have been compared: the rms differences in main-chain and side-chain positions are 0.25 and 0.69 A, respectively, both practically within error of the determinations. The largest deviations in the binding site are due to different crystal packing interactions. Thus, the lysine-binding site appears to be preformed, and lysine binding does not require conformational changes of the host. The results of NMR studies of lysine binding with K4 are correlated with the structure of K4-ACA and agree well.

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
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
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D014961	X-Ray Diffraction	The scattering of x-rays by matter, especially crystals, with accompanying variation in intensity due to interference effects. Analysis of the crystal structure of materials is performed by passing x-rays through them and registering the diffraction image of the rays (CRYSTALLOGRAPHY, X-RAY). (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Xray Diffraction,Diffraction, X-Ray,Diffraction, Xray,Diffractions, X-Ray,Diffractions, Xray,X Ray Diffraction,X-Ray Diffractions,Xray Diffractions
D015119	Aminocaproic Acid	An antifibrinolytic agent that acts by inhibiting plasminogen activators which have fibrinolytic properties.	6-Aminocaproic Acid,6-Aminohexanoic Acid,epsilon-Aminocaproic Acid,Amicar,CY-116,Capralense,Capramol,Caproamin,Caprocid,Caprolest,Epsamon,Epsikapron,Hemocaprol,Hexalense,6 Aminocaproic Acid,6 Aminohexanoic Acid,CY 116,CY116,epsilon Aminocaproic Acid