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

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 o...

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Bibliographic Details
Published in:Biochemistry (Easton) 1991-10, Vol.30 (43), p.10589-10594
Main Authors: Wu, Tswei Ping, Padmanabhan, Kaillathe, Tulinsky, A, Mulichak, Anne M
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Aminocaproic Acid - chemistry
Binding Sites
Biological and medical sciences
Crystalline structure
epsilon -aminocaproic acid
Fundamental and applied biological sciences. Psychology
Humans
Lysine - metabolism
Models, Molecular
Molecular biophysics
Molecular Sequence Data
Peptide Fragments - chemistry
Plasminogen - chemistry
Structure in molecular biology
X-Ray Diffraction
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Summary: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.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00107a030