Structural/functional properties of the Glu1‐HSer57 N‐terminal fragment of human plasminogen: Conformational characterization and interaction with kringle domains

An, Seong Soo A.; Martí, Daniel; Carreño, Cristina; Alberício, Fernando; Schaller, Johann; Llinás, Miguel

doi:10.1002/pro.5560070910

Cited by 13 publications

(33 citation statements)

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“…As reported (An et al, 1998), the Glul-HSer57 fragment of NTP (CB-NTP) interacts with the Pgn rK1, rK2, K4, and K5 domains. The aromatic LBS residues, Phe36, Trp25, Trp62, Phe/Tyr64, Trp72, and Tyr74 (kringle residue numbering convention), are consistently perturbed by ligand complexation and their 'H-NMR chemical shifts can be monitored to detect the interaction.…”

Section: Resultsmentioning

confidence: 68%

“…The aromatic LBS residues, Phe36, Trp25, Trp62, Phe/Tyr64, Trp72, and Tyr74 (kringle residue numbering convention), are consistently perturbed by ligand complexation and their 'H-NMR chemical shifts can be monitored to detect the interaction. As ranked by binding affinity, CB-NTP interacts with (An et al, 1998). Hence, we have selected K4 for further binding studies centered on synthetic, lysine-containing peptides that replicate segments within NTP.…”

Section: Resultsmentioning

confidence: 99%

“…We found that the interaction of K4 with ( I 3) is marginal ( K , -0.05 mM") and with (14) nil. Hence, we con- Figure 1 for K4, or reported in the accompanying paper (CB-NTP) (An et al, 1998).…”

Section: Peptides Containing Internal Arg Residue(s)mentioning

confidence: 87%

“…rK1 (K, -4.6 mM"), rK2 (KO -3.3 mM"), and K5 (K, -2.3 mM") (An et al, 1998). The kringle binding interactions of L-NTP are also of higher affinity than those measured for the N"-blocked, C'-blocked Arg or Lys ligands AcLysOMe (K, < 0.3 mM") and AcArgOMe (K, < 0.3 mM") (Marti et al, 1997), supporting structural factor(s) within L-NTP as defining the affinity of the Lys50 segment for the lysine-binding Pgn kringles.…”

Section: L-ntp Binding To Kringle I Kringle 2 and Kringlementioning

confidence: 99%

“…In an accompanying paper (An et al, 1998), we present 'H-NMR spectroscopic evidence indicating that CB-NTP interacts with recombinant K1 (rKl), rK2, K4, and K5, all lysine-binding kringles, with K4 exhibiting a somewhat higher affinity, while rK3, which is devoid of lysine binding capability (Sohndel et al, 1996), fails to interact. Based on similar experiments, it was previously demonstrated (Ramesh et al, 1995) that AFQYHSKSO, (K,,) values in the 2.5-X.5 m M -' range.…”

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confidence: 99%

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Lysine‐50 is a likely site for anchoring the plasminogen N‐terminal peptide to lysine‐binding kringles

Carreño

Martí

et al. 1998

Protein Science

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Interactions between the kringle 4 (K4) domain of human plasminogen (Pgn) and segments of the N-terminal GlulLys77 peptide (NTP) have been investigated via 'H-NMR at 500 MHz. NTP peptide stretches devoid of Lys residues but carrying an internal Arg residue show negligible affinity toward K4 (equilibrium association constant K, < 0.05 mM"). In contrast, while most fragments containing an internal Lys residue exhibit affinities comparable to that shown by the blocked Lys derivative Ne-acetyl-L-lysine-methyl ester (K, -0.2 mM-'), peptides encompassing Lys50 consistently show higher K, values. Among the investigated linear peptides, N"-acetyl-Ala-Phe-Tyr-His-Ser-Ser-Lys50-Glu-Gln-NH2 (AcAFYHSKSOEQ-NH,) exhibits the strongest interaction with K4 (KO -1.4 mM"), followed by AcYHSKSOEQ-NH2 (K, -0.9 mM"). Relative to the wild-type sequence, mutated hexapeptides exhibit lesser affinity for K4. When a Lys50 + Ser mutation was introduced (* AcYHSSSOEQ-NH,), binding was abolished.The Ile27-Ile56 construct (L-NTP) contains the Lys50 site within a loop constrained by two cystine bridges. The propensity of recombinant Pgn K1 (rKI) and K2 (rK2) modules, and of Pgn fragments encompassing the intact K4 and K5 domains, for binding L-NTP, was investigated. We find that L-NTP interacts with rK1, rK2, K4, and K5"all lysine-binding kringles-in a fashion that closely mimics what has been observed for the Glul-HSer57 N-terminal fragment of Pgn (CB-NTP). Thus, both the constellation of kringle lysine binding site (LBS) aromatic residues that are perturbed upon complexation of L-NTP and magnitudes of kringle-L-NTP binding affinities (rK1, K, -4.3 mM" ; rK2, K, -3.7 mM" ; K4, K, -6.4 mM" ; and K5, K, -2.1 mM-' ) are essentially the same as for the corresponding kringle-CB-NTP pairs. Molecular modeling studies suggest that the GIu39-Lys50 stretch in NTP generates an area that complements, both topologically and electrostatically, the solvent-exposed kringle LBS surface.

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Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Peptides Containing Internal Arg Residue(s)mentioning

confidence: 87%

Section: L-ntp Binding To Kringle I Kringle 2 and Kringlementioning

confidence: 99%

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confidence: 99%

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