1OXO

ASPARTATE AMINOTRANSFERASE, H-ASP COMPLEX, OPEN CONFORMATION


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal structures and solution studies of oxime adducts of mitochondrial aspartate aminotransferase.

Markovic-Housley, Z.Schirmer, T.Hohenester, E.Khomutov, A.R.Khomutov, R.M.Karpeisky, M.Y.Sandmeier, E.Christen, P.Jansonius, J.N.

(1996) Eur J Biochem 236: 1025-1032

  • DOI: https://doi.org/10.1111/j.1432-1033.1996.01025.x
  • Primary Citation of Related Structures:  
    1OXO, 1OXP

  • PubMed Abstract: 

    The interaction of mitochondrial aspartate aminotransferase with hydroxylamine and five derivatives (in which the hydroxyl hydrogen is replaced by the side chain of naturally occurring amino acids) was investigated by X-ray diffraction as well as by kinetic and spectral measurements with the enzyme in solution. The inhibitors react with pyridoxal 5'-phosphate in the enzyme active site, both in solution and in the crystalline state, in a reversible single-step reaction forming spectrally distinct oxime adducts. Dissociation constants determined in solution range from 10(-8) M to 10(-6) M depending on the nature of the side-chain group. The crystal structures of the adducts of mitochondrial aspartate aminotransferase with the monocarboxylic analogue of L-aspartate in the open and closed enzyme conformation were determined at 0.23-nm and 0.25-nm resolution, respectively. This inhibitor binds to both the open and closed crystal forms of the enzyme without disturbing the crystalline order. Small differences in the conformation of the cofactor pyridoxal phosphate were detected between the omega-carboxylate of the inhibitor and Arg292 of the neighbouring subunit is mainly responsible for the attainment of near-coplanarity of the aldimine bond with the pyridine ring in the oxime adducts. Studies with a fluorescent probe aimed to detect shifts in the open/closed conformational equilibrium of the enzyme in oxime complexes showed that the hydroxylamine-derived inhibitors, even those containing a carboxylate group, do not induce the 'domain closure' in solution. This is probably due to the absence of the alpha-carboxylate group in the monocarboxylic hydroxylamine-derived inhibitors, emphasizing that both carboxylates of the substrates L-Asp and L-Glu are essential for stabilizing the closed form of aspartate aminotransferase.


  • Organizational Affiliation

    Abteilung Strukturbiologie, Biozentrum der Universität Basel, Basel, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ASPARTATE AMINOTRANSFERASE
A, B
401Gallus gallusMutation(s): 0 
EC: 2.6.1.1
UniProt
Find proteins for P00508 (Gallus gallus)
Explore P00508 
Go to UniProtKB:  P00508
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00508
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
IK2
Query on IK2

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
4'-DEOXY-4'-ACETYLYAMINO-PYRIDOXAL-5'-PHOSPHATE
C10 H15 N2 O8 P
QYKRUCBLHROXCK-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.7α = 85.2
b = 58.8β = 109.2
c = 76γ = 115.7
Software Package:
Software NamePurpose
PROLSQrefinement
MADNESdata reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1996-06-10
    Type: Initial release
  • Version 1.1: 2008-03-24
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-04-18
    Changes: Advisory, Data collection, Other
  • Version 1.4: 2024-02-14
    Changes: Advisory, Data collection, Database references, Derived calculations