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Titolo:
Inhibition of the aminopeptidase from Aeromonas proteolytica by L-leucinephosphonic acid. Spectroscopic and crystallographic characterization of the transition state of peptide hydrolysis
Autore:
Stamper, C; Bennett, B; Edwards, T; Holz, RC; Ringe, D; Petsko, C;
Indirizzi:
Utah State Univ, Dept Chem & Biochem, Logan, UT 84322 USA Utah State UnivLogan UT USA 84322 pt Chem & Biochem, Logan, UT 84322 USA Brandeis Univ, Dept Biochem, Program Biophys & Struct Biol, Waltham, MA 02254 USA Brandeis Univ Waltham MA USA 02254 s & Struct Biol, Waltham, MA 02254 USA Brandeis Univ, Dept Chem, Waltham, MA 02254 USA Brandeis Univ Waltham MA USA 02254 Univ, Dept Chem, Waltham, MA 02254 USA Brandeis Univ, Rosenstiel Basic Med Res Ctr, Waltham, MA 02254 USA Brandeis Univ Waltham MA USA 02254 sic Med Res Ctr, Waltham, MA 02254 USA
Titolo Testata:
BIOCHEMISTRY
fascicolo: 24, volume: 40, anno: 2001,
pagine: 7035 - 7046
SICI:
0006-2960(20010619)40:24<7035:IOTAFA>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
ELECTRON-PARAMAGNETIC-RESONANCE; LENS LEUCINE AMINOPEPTIDASE; MAGNETIC CIRCULAR-DICHROISM; DEPENDENT BETA-LACTAMASE; X-RAY STRUCTURE; CRYSTAL-STRUCTURE; METHIONINE AMINOPEPTIDASE; ANGSTROM RESOLUTION; ESCHERICHIA-COLI; CATALYTIC MECHANISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
59
Recensione:
Indirizzi per estratti:
Indirizzo: Petsko, C Utah State Univ, Dept Chem & Biochem, Logan, UT 84322 USA Utah State Univ Logan UT USA 84322 Biochem, Logan, UT 84322 USA
Citazione:
C. Stamper et al., "Inhibition of the aminopeptidase from Aeromonas proteolytica by L-leucinephosphonic acid. Spectroscopic and crystallographic characterization of the transition state of peptide hydrolysis", BIOCHEM, 40(24), 2001, pp. 7035-7046

Abstract

The nature of the interaction of the transition-state analogue inhibitor L-leucinephosphonic acid (LPA) with the leucine aminopeptidase from Aeromonas proteolytica (AAP) was investigated. LPA was shown to be a competitive inhibitor at pH 8.0 with a K-i of 6.6 muM. Electronic absorption spectra, recorded at pH 7.5 of [CoCo(AAP)], [CoZn(AAP)], and [ZnCo(AAP)] upon addition of LPA suggest that LPA interacts with both metal ions in the dinuclear active site, EPR studies on the Co(II)-substituted forms of AAP revealed that the environments of the Co(II) lions in both [CoZn(AAP)] and [ZnCo(AAP)] become highly asymmetric and constrained upon the addition of LPA and clearlyindicate that LPA interacts with both metal ions. The X-ray crystal structure of AAP complexed with LPA was determined at 2.1 Angstrom, resolution. The X-ray crystallographic data indicate that LPA interacts with both metal centers in the dinuclear active site of AAP and a single oxygen atom bridgeis absent. Thus, LPA binds to the dinuclear active site of AAP as an eta -1,2-mu -phosphonate with one ligand to the second metal ion provided by theN-terminal amine. A structural comparison of the binding of phosphonate-containing transition-state analogues to the mono- and bimetallic peptidases provides insight into the requirement for the second metal ion in bridged bimetallic peptidases. On the basis of the results obtained from the spectroscopic and X-ray crystallographic data presented herein along with previously reported mechanistic data for AAP, a new catalytic mechanism for the hydrolysis reaction catalyzed by AAP is proposed.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 13:39:44