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Synthetic peptides as structural maquettes of Angiotensin-I converting enzyme catalytic sites.

Spyranti Z, Galanis AS, Pairas G, Spyroulias GA, Manessi-Zoupa E, Cordopatis P - Bioinorg Chem Appl (2010)

Bottom Line: The rational design of synthetic peptides is proposed as an efficient strategy for the structural investigation of crucial protein domains difficult to be produced.Only after half a century since the function of ACE was first reported, was its crystal structure solved.Structural investigations of the synthetic peptides, representing the two different somatic isoform active sites, through circular dichroism and NMR experiments are reported.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, University of Patras, GR-26504, Patras, Greece.

ABSTRACT
The rational design of synthetic peptides is proposed as an efficient strategy for the structural investigation of crucial protein domains difficult to be produced. Only after half a century since the function of ACE was first reported, was its crystal structure solved. The main obstacle to be overcome for the determination of the high resolution structure was the crystallization of the highly hydrophobic transmembrane domain. Following our previous work, synthetic peptides and Zinc(II) metal ions are used to build structural maquettes of the two Zn-catalytic active sites of the ACE somatic isoform. Structural investigations of the synthetic peptides, representing the two different somatic isoform active sites, through circular dichroism and NMR experiments are reported.

No MeSH data available.


(a) Ensemble of DYANA 30 best models of the Zn2+-ACEN(37) (corresponds to His360-Ala396 of the human somatic form) calculated with NMR data. (b) Ribbon diagram of Zn2+-ACEN(37) peptide.
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fig6: (a) Ensemble of DYANA 30 best models of the Zn2+-ACEN(37) (corresponds to His360-Ala396 of the human somatic form) calculated with NMR data. (b) Ribbon diagram of Zn2+-ACEN(37) peptide.

Mentions: As far as the N-terminal Zn-binding motif of ACEN(37) peptide, which contains the two histidyl ligands, is concerned, no definite conformation could be determined due to conformational averaging. A 7-residue fragment close to the N-terminal (Gln8-Asp15) adopts helical structure, which consists partly of an α-helix for the 8-11 fragment and of a short 310-helix for the rest of the four-residue segment. A second fragment comprised of 7 residues close to peptide C-terminal (His29- Leu36) adopts a well formed α-helical structure. As far as the intermediate fragment of the 23-residue spacer between the two binding motifs is concerned, no helical conformation has been identified. The proximity of the two “active sites helices” is manifested by long-range NOEs concerning backbone and side-chain protons of His2–Glu30, Gly5–Gly34, Tyr9–Phe28 see (Figure  S1) in Supplementary Material available online at doi: 10.1155/2010/820476, as well as Tyr9–His30 (Figure 6).


Synthetic peptides as structural maquettes of Angiotensin-I converting enzyme catalytic sites.

Spyranti Z, Galanis AS, Pairas G, Spyroulias GA, Manessi-Zoupa E, Cordopatis P - Bioinorg Chem Appl (2010)

(a) Ensemble of DYANA 30 best models of the Zn2+-ACEN(37) (corresponds to His360-Ala396 of the human somatic form) calculated with NMR data. (b) Ribbon diagram of Zn2+-ACEN(37) peptide.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902127&req=5

fig6: (a) Ensemble of DYANA 30 best models of the Zn2+-ACEN(37) (corresponds to His360-Ala396 of the human somatic form) calculated with NMR data. (b) Ribbon diagram of Zn2+-ACEN(37) peptide.
Mentions: As far as the N-terminal Zn-binding motif of ACEN(37) peptide, which contains the two histidyl ligands, is concerned, no definite conformation could be determined due to conformational averaging. A 7-residue fragment close to the N-terminal (Gln8-Asp15) adopts helical structure, which consists partly of an α-helix for the 8-11 fragment and of a short 310-helix for the rest of the four-residue segment. A second fragment comprised of 7 residues close to peptide C-terminal (His29- Leu36) adopts a well formed α-helical structure. As far as the intermediate fragment of the 23-residue spacer between the two binding motifs is concerned, no helical conformation has been identified. The proximity of the two “active sites helices” is manifested by long-range NOEs concerning backbone and side-chain protons of His2–Glu30, Gly5–Gly34, Tyr9–Phe28 see (Figure  S1) in Supplementary Material available online at doi: 10.1155/2010/820476, as well as Tyr9–His30 (Figure 6).

Bottom Line: The rational design of synthetic peptides is proposed as an efficient strategy for the structural investigation of crucial protein domains difficult to be produced.Only after half a century since the function of ACE was first reported, was its crystal structure solved.Structural investigations of the synthetic peptides, representing the two different somatic isoform active sites, through circular dichroism and NMR experiments are reported.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, University of Patras, GR-26504, Patras, Greece.

ABSTRACT
The rational design of synthetic peptides is proposed as an efficient strategy for the structural investigation of crucial protein domains difficult to be produced. Only after half a century since the function of ACE was first reported, was its crystal structure solved. The main obstacle to be overcome for the determination of the high resolution structure was the crystallization of the highly hydrophobic transmembrane domain. Following our previous work, synthetic peptides and Zinc(II) metal ions are used to build structural maquettes of the two Zn-catalytic active sites of the ACE somatic isoform. Structural investigations of the synthetic peptides, representing the two different somatic isoform active sites, through circular dichroism and NMR experiments are reported.

No MeSH data available.