Document Detail


Ligand specificity of human plasminogen kringle 4.
MedLine Citation:
PMID:  1657159     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The ligand specificity of the human plasminogen kringle 4 was characterized in terms of ligand size, aromatic/aliphatic character, and ionic charge distribution. The binding of the following ligands was investigated via 1H NMR spectroscopy, and their equilibrium association constants (Ka) were determined: (1) p-aminomethylbenzoic acid (Ka approximately 4.8 mM-1), (2) benzylamine (Ka approximately 0.2 mM-1), (3) l-aminohexane (Ka approximately 0.07 mM-1), (4) 7-aminoheptanoic acid (Ka approximately 6.6 mM-1), (5) 5-aminopentanoic acid (Ka approximately 16 mM-1), (6) N alpha-acetyl-L-arginine (Ka approximately 0.3 mM-1), and (7) N alpha-acetyl-L-arginine methyl ester (Ka approximately 0.08 mM-1). Benzamidine and L-arginine do not bind measurably to kringle 4. We have also established that 1-hexanoic acid and 4-methylbenzoic acid do not interact significantly with kringle 4 (Ka less than 0.05 mM-1). The Trp62 resonances were found to be quite sensitive to aromatic ligands as well as to aliphatic ligand length. Phe64 is similarly sensitive to the ligand aromatic/aliphatic character and chain length and to the identity of the ligand anionic group. His31 and His33 do not respond significantly to variations in ligand structure, although they are perturbed by aromatic and aliphatic effectors. The perturbations induced by the arginine derivatives on these residues show that these compounds interact with the lysine-binding site (LBS) of kringle 4. The LBS was further characterized using 2D NMR studies of a kringle 4/trans-(aminomethyl)cyclohexanecarboxylic acid (AMCHA) complex. A complete assignment of the AMCHA spectrum in the bound state was achieved. This enabled the unambiguous identification of intermolecular contact points between the central AMCHA protons and Trp62 and Trp72. A model based on the X-ray crystallographic structure of kringle 4, incorporating these constraints, has been derived.
Authors:
M R Rejante; I J Byeon; M Llinás
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  30     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  1991 Nov 
Date Detail:
Created Date:  1991-12-20     Completed Date:  1991-12-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  11081-92     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213-3890.
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MeSH Terms
Descriptor/Qualifier:
4-Aminobenzoic Acid / analogs & derivatives,  chemistry
6-Aminocaproic Acid / analogs & derivatives
Benzoates / chemistry
Benzoic Acids*
Benzylamines / chemistry
Humans
Macromolecular Substances
Magnetic Resonance Spectroscopy
Peptide Fragments / chemistry*
Plasminogen / chemistry*
Protein Binding
Substrate Specificity
Tranexamic Acid / chemistry
Grant Support
ID/Acronym/Agency:
1P41RR06009/RR/NCRR NIH HHS; HL-29409/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Benzoates; 0/Benzoic Acids; 0/Benzylamines; 0/Macromolecular Substances; 0/Peptide Fragments; 1197-18-8/Tranexamic Acid; 150-13-0/4-Aminobenzoic Acid; 56-91-7/4-aminomethylbenzoic acid; 60-32-2/6-Aminocaproic Acid; 9001-91-6/Plasminogen; 99-94-5/4-toluic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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