1i71
From Proteopedia
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HIGH RESOLUTION CRYSTAL STRUCTURE OF APOLIPOPROTEIN(A) KRINGLE IV TYPE 7: INSIGHTS INTO LIGAND BINDING
Contents |
Overview
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 KIV(1), to KIV(10)) 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. KIV(10) represents the, high-affinity lysine-binding site (LBS) of apo(a); a weak LBS is predicted, in each of KIV(5)-KIV(8) and has been directly demonstrated in KIV(7). The, present study describes the first crystal structure of apo(a) KIV(7), refined to a resolution of 1.45 A, representing the highest resolution for, a kringle structure determined to date. A critical substitution of Tyr-62, in KIV(7) for the corresponding Phe-62 residue in KIV(10), in conjunction, with the presence of Arg-35 in KIV(7), 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 KIV(7) relative to that of KIV(10).
Disease
Known diseases associated with this structure: Coronary artery disease, susceptibility to OMIM:[152200], LPA deficiency, congenital OMIM:[152200]
About this Structure
1I71 is a Single protein structure of sequence from Homo sapiens with SO4 as ligand. Full crystallographic information is available from OCA.
Reference
High-resolution crystal structure of apolipoprotein(a) kringle IV type 7: insights into ligand binding., Ye Q, Rahman MN, Koschinsky ML, Jia Z, Protein Sci. 2001 Jun;10(6):1124-9. PMID:11369850
Page seeded by OCA on Mon Nov 12 17:26:45 2007
