Solid-phase synthesis and conformational properties of angiotensin converting enzyme catalytic-site peptides: the basis for a structural study on the enzyme-substrate interaction.
The solution NMR conformational properties of two angiotensin converting enzyme (ACE) Zn catalytic-site 36-residue peptides, with the general sequence HEMGHX23EAIGDX3, synthesized through solid-phase 9-fluorenylmethoxycarbonyl (Fmoc) chemistry, is reported. The 1H resonance assignment of Zn-bound peptides is presented and the characteristic features of the NMR solution models of the two ACE Zn(II)-bound peptides are reported. The solid-state and solution structures of the ACE C-domain catalytic site are compared while biologically important structural similarities and differences of the N- and C-terminal catalytic sites are discussed. Additionally, the structural features of the ACE substrate, the angiotensin I (AI) decapeptide, are studied using NMR spectroscopy, in order to set the structural basis for the ACE-substrate interaction in solution.
Galanis
Athanassios S
AS
Department of Pharmacy, University of Patras, GR-26504, Patras, Greece.
Spyroulias
Georgios A
GA
Pairas
George
G
Manessi-Zoupa
Evy
E
Cordopatis
Paul
P
D000595:Amino Acid Sequence; D000803:Angiotensin I / Q000737:chemistry; D000818:Animals; D020134:Catalytic Domain; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry*; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry*; D011487:Protein Conformation; D012996:Solutions; D013379:Substrate Specificity; D015032:Zinc / Q000737:chemistry
D010446:Peptide Fragments; D012996:Solutions; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D015032:Zinc