Proton NMR studies of aliphatic ligand binding to human plasminogen kringle 4

Journal Article · Tue Feb 07 04:00:00 EST 1989 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00429a064· OSTI ID:5640710

Petros, A M; Ramesh, V; Llinas, M ^[1]

---

1. Carnegie Mellon Univ., Pittsburgh, PA (USA)

A detailed {sup 1}H NMR analysis of ligand binding to the human plasminogen kringle 4 domain has been carried out at 300 MHz. The ligands that were investigated are N{sup {alpha}}-acetyl-L-lysine, L-lysine methyl ester, N{sup {alpha}}-acetyl-L-lysine methyl ester, L-lysine hydroxamic acid, trans-(aminomethyl)cyclohexanecarboxylic acid (AMCHA), and 4-(aminomethyl)bicyclo(2.2.2)octane-1-carboxylic acid (AMBOC). Specific ligand-binding effects were detected via two-dimensional COSY experiments. The side chains that are the most perturbed by ligand presence are those from Trp{sup 62}, Phe{sup 64}, and Trp{sup 72}. Ligand-kringle saturation transfer (Overhauser) experiments show that the aromatic rings from these three residues are in direct contact with the ligand. These results add support to a previously reported model of the kringle 4 lysine-binding site by which these aromatic groups are assigned a key role in establishing hydrophobic interactions with the ligand molecule. Equilibrium association constants (K{sub a}) and kinetic rate constants (k{sub on}, k{sub off}) were determined for the binding of the various linear and cyclic ligands to kringle 4. The numerical data are discussed in terms of optimal ligand structure and requirements for fibrin binding in vivo.

• OSTI ID: 5640710
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:3; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
ANIMALS
BARYONS
BIOCHEMISTRY
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHEMISTRY
COAGULANTS
CROSS-LINKING
DECOMPOSITION
DRUGS
ELEMENTARY PARTICLES
FERMIONS
FIBRIN
FIBRINOLYSIS
FIBRINOLYTIC AGENTS
HADRONS
HEMATOLOGIC AGENTS
HEMOSTATICS
LIGANDS
LYSINE
MAGNETIC RESONANCE
MAMMALS
MAN
MOLECULAR STRUCTURE
NUCLEAR MAGNETIC RESONANCE
NUCLEONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PLASMINOGEN
POLYMERIZATION
PRIMATES
PROTEINS
PROTEOLYSIS
PROTONS
RESONANCE
SCLEROPROTEINS
VERTEBRATES