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| | {{STRUCTURE_1txr| PDB=1txr | SCENE= }} | | {{STRUCTURE_1txr| PDB=1txr | SCENE= }} |
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| - | '''X-ray crystal structure of bestatin bound to AAP'''
| + | ===X-ray crystal structure of bestatin bound to AAP=== |
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| - | ==Overview==
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| - | Binding of the competitive, slow-binding inhibitor bestatin ([(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoy]-leucine) to the aminopeptidase from Aeromonas proteolytica (AAP) was examined by both spectroscopic and crystallographic methods. Electronic absorption spectra of the catalytically competent [Co_(AAP)], [CoCo(AAP)], and [ZnCo(AAP)] enzymes recorded in the presence of bestatin revealed that both of the divalent metal ions in AAP are involved in binding bestatin. The electron paramagnetic resonance (EPR) spectrum of the [CoCo(AAP)]-bestatin complex exhibited no observable perpendicular- or parallel-mode signal. These data indicate that the two Co(II) ions in AAP are antiferromagnetically coupled yielding an S = 0 ground state and suggest that a single oxygen atom bridges between the two divalent metal ions. The EPR data obtained for [CoZn(AAP)] and [ZnCo(AAP)] confirm that bestatin interacts with both metal ions. The X-ray crystal structure of the [ZnZn(AAP)]-bestatin complex was solved to 2.0 A resolution. Both side chains of bestatin occupy a well-defined hydrophobic pocket that is adjacent to the dinuclear Zn(II) active site. The amino acid residues ligated to the dizinc(II) cluster in AAP are identical to those in the native structure with only minor perturbations in bond length. The alkoxide oxygen of bestatin bridges between the two Zn(II) ions in the active site, displacing the bridging water molecule observed in the native [ZnZn(AAP)] structure. The M-M distances observed in the AAP-bestatin complex and native AAP are identical (3.5 A) with alkoxide oxygen atom distances of 2.1 and 1.9 A from Zn1 and Zn2, respectively. Interestingly, the backbone carbonyl oxygen atom of bestatin is coordinated to Znl at a distance of 2.3 A. In addition, the NH(2) group of bestatin, which mimics the N-terminal amine group of an incoming peptide, binds to Zn2 with a bond distance of 2.3 A. A combination of the spectroscopic and X-ray crystallographic data presented herein with the previously reported mechanistic data for AAP has provided additional insight into the substrate-binding step of peptide hydrolysis as well as insight into important small molecule features for inhibitor design.
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| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15274616 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15274616}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Aminopeptidase]] | | [[Category: Aminopeptidase]] |
| | [[Category: Bestatin]] | | [[Category: Bestatin]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:29:55 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:36:55 2008'' |
Revision as of 15:36, 27 July 2008
Template:STRUCTURE 1txr
X-ray crystal structure of bestatin bound to AAP
Template:ABSTRACT PUBMED 15274616
About this Structure
1TXR is a Single protein structure of sequence from Vibrio proteolyticus. Full crystallographic information is available from OCA.
Reference
Spectroscopic and X-ray crystallographic characterization of bestatin bound to the aminopeptidase from Aeromonas (Vibrio) proteolytica., Stamper CC, Bienvenue DL, Bennett B, Ringe D, Petsko GA, Holz RC, Biochemistry. 2004 Aug 3;43(30):9620-8. PMID:15274616
Page seeded by OCA on Sun Jul 27 18:36:55 2008
