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Titolo:
High-resolution crystal structure of apolipoprotein(a) kringle IV type 7: Insights into ligand binding
Autore:
Ye, QL; Rahman, MN; Koschinsky, ML; Jia, ZC;
Indirizzi:
Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada Queens Univ Kingston ON Canada K7L 3N6 chem, Kingston, ON K7L 3N6, Canada
Titolo Testata:
PROTEIN SCIENCE
fascicolo: 6, volume: 10, anno: 2001,
pagine: 1124 - 1129
SICI:
0961-8368(200106)10:6<1124:HCSOAK>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
RHESUS-MONKEY LIPOPROTEIN(A); AMINO ACID LIGANDS; HUMAN PLASMINOGEN; DOMAIN; SITES; DETERMINANTS; PHENOTYPES; SEQUENCES; RELEVANCE; EVOLUTION;
Keywords:
apolipoprotein(a); kringle; lysine binding; crystal structure;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Jia, ZC Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada Queens Univ Kingston ON Canada K7L 3N6 ngston, ON K7L 3N6, Canada
Citazione:
Q.L. Ye et al., "High-resolution crystal structure of apolipoprotein(a) kringle IV type 7: Insights into ligand binding", PROTEIN SCI, 10(6), 2001, pp. 1124-1129

Abstract

Apolipoprotein(a) [apo(a)] consists of a series of tandemly repeated modules known as kringles that are commonly found in many proteins involved in the fibrinolytic and coagulation cascades, such as plasminogen and thrombin,respectively. Specifically, apo(a) contains multiple tandem repeats of domains similar to plasminogen kringle IV (designated as KIV1 to KIV10) followed by sequences similar to the kringle V and protease domains of plasminogen. The KIV domains of apo(a) differ with respect to their ability to bind lysine or lysine analogs. KIV10 represents the high-affinity lysine-binding site (LBS) of apo(a); a weak LBS is predicted in each of KIV5-KIV8 and has been directly demonstrated in KIV7. The present study describes the first crystal structure of apo(a) KIV7, refined to a resolution of 1.45 Angstrom, representing the highest resolution for a kringle structure determined to date. A critical substitution of Tyr-62 in KIV7 for the corresponding Phe-62residue in KIV10, in conjunction with the presence of Arg-35 in KIV7, results in the formation of a unique network of hydrogen bonds and electrostatic interactions between key LBS residues (Arg-35, Tyr-62, Asp-54) and a peripheral tyrosine residue (Tyr-40). These interactions restrain the flexibility of key LBS residues (Arg-35, Asp-54) and, in turn, reduce their adaptability in accommodating lysine and its analogs. Steric hindrance involving Tyr-62, as well as the elimination of critical ligand-stabilizing interactions within the LBS are also consequences of this interaction network. Thus, these subtle yet critical structural features are responsible for the weak lysine-binding affinity exhibited by KIV7 relative to that of KIV10.

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Documento generato il 28/01/20 alle ore 14:45:42