PDBsum entry 1ama

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Transferase(aminotransferase) PDB id
Protein chain
401 a.a. *
Waters ×312
* Residue conservation analysis
PDB id:
Name: Transferase(aminotransferase)
Title: Domain closure in mitochondrial aspartate aminotransferase
Structure: Aspartate aminotransferase. Chain: a. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Organ: heart. Expressed in: unidentified. Expression_system_taxid: 32644
Biol. unit: Dimer (from PQS)
2.30Å     R-factor:   0.159    
Authors: M.G.Vincent,J.-C.Genovesio-Taverne,J.N.Jansonius
Key ref:
C.A.McPhalen et al. (1992). Domain closure in mitochondrial aspartate aminotransferase. J Mol Biol, 227, 197-213. PubMed id: 1522585 DOI: 10.1016/0022-2836(92)90691-C
05-Feb-92     Release date:   31-Oct-93    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P00508  (AATM_CHICK) -  Aspartate aminotransferase, mitochondrial
423 a.a.
401 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: E.C.  - Aspartate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate
+ 2-oxoglutarate
= oxaloacetate
+ L-glutamate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PLA) matches with 57.69% similarity
   Enzyme class 2: E.C.  - Kynurenine--oxoglutarate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Reaction: L-kynurenine + 2-oxoglutarate = 4-(2-aminophenyl)-2,4-dioxobutanoate + L-glutamate
+ 2-oxoglutarate
= 4-(2-aminophenyl)-2,4-dioxobutanoate
+ L-glutamate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   2 terms 
  Biological process     small molecule metabolic process   9 terms 
  Biochemical function     catalytic activity     8 terms  


DOI no: 10.1016/0022-2836(92)90691-C J Mol Biol 227:197-213 (1992)
PubMed id: 1522585  
Domain closure in mitochondrial aspartate aminotransferase.
C.A.McPhalen, M.G.Vincent, D.Picot, J.N.Jansonius, A.M.Lesk, C.Chothia.
The subunits of the dimeric enzyme aspartate aminotransferase have two domains: one large and one small. The active site lies in a cavity that is close to both the subunit interface and the interface between the two domains. On binding the substrate the domains close together. This closure completely buries the substrate in the active site and moves two arginine side-chains so they form salt bridges with carboxylate groups of the substrate. The salt bridges hold the substrate close to the pyridoxal 5'-phosphate cofactor and in the right position and orientation for the catalysis of the transamination reaction. We describe here the structural changes that produce the domain movements and the closure of the active site. Structural changes occur at the interface between the domains and within the small domain itself. On closure, the core of the small domain rotates by 13 degrees relative to the large domain. Two other regions of the small domain, which form part of the active site, move somewhat differently. A loop, residues 39 to 49, above the active site moves about 1 A less than the core of the small domain. A helix within the small domain forms the "door" of the active site. It moves with the core of the small domain and, in addition, shifts by 1.2 A, rotates by 10 degrees, and switches its first turn from the alpha to the 3(10) conformation. This results in the helix closing the active site. The domain movements are produced by a co-ordinated series of small changes. Within one subunit the polypeptide chain passes twice between the large and small domains. One link involves a peptide in an extended conformation. The second link is in the middle of a long helix that spans both domains. At the interface this helix is kinked and, on closure, the angle of the kink changes to accommodate the movement of the small domain. The interface between the domains is formed by 15 residues in the large domain packing against 12 residues in the small domain and the manner in which these residues pack is essentially the same in the open and closed structures. Domain movements involve changes in the main-chain and side-chain torsion angles in the residues on both sides of the interface. Most of these changes are small; only a few side-chains switch to new conformations.(ABSTRACT TRUNCATED AT 400 WORDS)
  Selected figure(s)  
Figure 1.
Fig. 1.
Figure 3.
Figure 3. he magnitude of the structural changes that occur on domain closure. (a) The differences in the positions of C'' atoms in the open and closed forms of AATase. The differences are those measured after the open and closed forms of the subunit have been superposed by a fit of the main-cain atoms in the large domain regions that have the same structure in the 2 forms (see the text and Fig. l(b)). (b) St ructural differences within the small domain tht occur on omain closure. The differences shown here are those found after the small domains in the open and closed forms of the subunit have been superposed by a fit of the regions that have the same structure in the 2 forms (see the text). Residues 15 to 31 iffer in position because thy move more than the core of the small domain; residues 39 to 47 differ because they move less (see the text).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1992, 227, 197-213) copyright 1992.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19917609 T.Lendrihas, G.A.Hunter, and G.C.Ferreira (2010).
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Mechanism for multiple-substrates recognition of alpha-aminoadipate aminotransferase from Thermus thermophilus.
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PDB codes: 2zp7 3cbf
18216238 G.M.Clayton, S.Altieri, L.Heginbotham, V.M.Unger, and J.H.Morais-Cabral (2008).
Structure of the transmembrane regions of a bacterial cyclic nucleotide-regulated channel.
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PDB codes: 2zd9 3beh
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Switching in of Ac-(Ala)10-NHMe at a solid surface.
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Crystal structure of Homo sapiens kynureninase.
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PDB code: 2hzp
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Structures of apo- and holo-tyrosine phenol-lyase reveal a catalytically critical closed conformation and suggest a mechanism for activation by K+ ions.
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PDB codes: 2ez1 2ez2
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3(10)-helices in proteins are parahelices.
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Directed evolution relieves product inhibition and confers in vivo function to a rationally designed tyrosine aminotransferase.
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12471605 A.Paiardini, G.Gianese, F.Bossa, and S.Pascarella (2003).
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The nature of the rate-limiting steps in the refolding of the cofactor-dependent protein aspartate aminotransferase.
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12717026 V.R.Sobrado, M.Montemartini-Kalisz, H.M.Kalisz, M.C.De La Fuente, H.J.Hecht, and C.Nowicki (2003).
Involvement of conserved asparagine and arginine residues from the N-terminal region in the catalytic mechanism of rat liver and Trypanosoma cruzi tyrosine aminotransferases.
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12119022 C.G.Cheong, J.C.Escalante-Semerena, and I.Rayment (2002).
Structural studies of the L-threonine-O-3-phosphate decarboxylase (CobD) enzyme from Salmonella enterica: the apo, substrate, and product-aldimine complexes.
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PDB codes: 1l4b 1l4e 1l4f 1l4g 1l4h 1l4k 1l4l 1l4m 1l4n 1l5f 1l5k 1l5l 1l5m 1l5n 1l5o 1lc5 1lc7 1lc8
12235163 E.B.Kuettner, R.Hilgenfeld, and M.S.Weiss (2002).
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PDB code: 1lk9
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Crystal structure of binary and ternary complexes of serine hydroxymethyltransferase from Bacillus stearothermophilus: insights into the catalytic mechanism.
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PDB codes: 1kkj 1kkp 1kl1 1kl2
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10212188 G.A.Hunter, and G.C.Ferreira (1999).
Pre-steady-state reaction of 5-aminolevulinate synthase. Evidence for a rate-determining product release.
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Functional and structural analysis of cis-proline mutants of Escherichia coli aspartate aminotransferase.
  Biochemistry, 38, 905-913.
PDB codes: 1bqa 1bqd
10026165 M.Bertoldi, P.Frigeri, M.Paci, and C.B.Voltattorni (1999).
Reaction specificity of native and nicked 3,4-dihydroxyphenylalanine decarboxylase.
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10601302 N.D.Lazo, and D.T.Downing (1999).
A mixture of alpha-helical and 3(10)-helical conformations for involucrin in the human epidermal corneocyte envelope provides a scaffold for the attachment of both lipids and proteins.
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Structural principles governing domain motions in proteins.
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Redesigning the substrate specificity of an enzyme by cumulative effects of the mutations of non-active site residues.
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PDB code: 1yoo
10029535 T.Nakai, K.Okada, S.Akutsu, I.Miyahara, S.Kawaguchi, R.Kato, S.Kuramitsu, and K.Hirotsu (1999).
Structure of Thermus thermophilus HB8 aspartate aminotransferase and its complex with maleate.
  Biochemistry, 38, 2413-2424.
PDB codes: 1bjw 1bkg
  10595543 W.Blankenfeldt, C.Nowicki, M.Montemartini-Kalisz, H.M.Kalisz, and H.J.Hecht (1999).
Crystal structure of Trypanosoma cruzi tyrosine aminotransferase: substrate specificity is influenced by cofactor binding mode.
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PDB code: 1bw0
9675237 A.Azzariti, R.A.Vacca, S.Giannattasio, R.S.Merafina, E.Marra, and S.Doonan (1998).
Kinetic properties and thermal stabilities of mutant forms of mitochondrial aspartate aminotransferase.
  Biochim Biophys Acta, 1386, 29-38.  
9761826 C.Nowicki, M.Montemartini, G.R.Hunter, W.Blankenfeldt, H.M.Kalisz, and H.J.Hecht (1998).
Crystallization and preliminary X-ray analysis of tyrosine aminotransferase from Trypanosoma cruzi epimastigotes.
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9914259 J.N.Jansonius (1998).
Structure, evolution and action of vitamin B6-dependent enzymes.
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Motifs and structural fold of the cofactor binding site of human glutamate decarboxylase.
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9722650 M.Gerstein, and W.Krebs (1998).
A database of macromolecular motions.
  Nucleic Acids Res, 26, 4280-4290.  
9660802 S.Kawaguchi, and S.Kuramitsu (1998).
Thermodynamics and molecular simulation analysis of hydrophobic substrate recognition by aminotransferases.
  J Biol Chem, 273, 18353-18364.  
9521707 S.Sun, R.F.Zabinski, and M.D.Toney (1998).
Reactions of alternate substrates demonstrate stereoelectronic control of reactivity in dialkylglycine decarboxylase.
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9792664 Y.Nobe, S.Kawaguchi, H.Ura, T.Nakai, K.Hirotsu, R.Kato, and S.Kuramitsu (1998).
The novel substrate recognition mechanism utilized by aspartate aminotransferase of the extreme thermophile Thermus thermophilus HB8.
  J Biol Chem, 273, 29554-29564.  
9012676 E.T.Mollova, D.E.Metzler, A.Kintanar, H.Kagamiyama, H.Hayashi, K.Hirotsu, and I.Miyahara (1997).
Use of 1H-15N heteronuclear multiple-quantum coherence NMR spectroscopy to study the active site of aspartate aminotransferase.
  Biochemistry, 36, 615-625.  
9012678 J.Hwa, R.Gaivin, J.E.Porter, and D.M.Perez (1997).
Synergism of constitutive activity in alpha 1-adrenergic receptor activation.
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9242917 M.Levitt, M.Gerstein, E.Huang, S.Subbiah, and J.Tsai (1997).
Protein folding: the endgame.
  Annu Rev Biochem, 66, 549-579.  
9211866 S.Rhee, M.M.Silva, C.C.Hyde, P.H.Rogers, C.M.Metzler, D.E.Metzler, and A.Arnone (1997).
Refinement and comparisons of the crystal structures of pig cytosolic aspartate aminotransferase and its complex with 2-methylaspartate.
  J Biol Chem, 272, 17293-17302.
PDB codes: 1ajr 1ajs
9370432 T.B.Woolf (1997).
Molecular dynamics of individual alpha-helices of bacteriorhodopsin in dimyristol phosphatidylocholine. I. Structure and dynamics.
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8856080 P.Kasper, M.Sterk, P.Christen, and H.Gehring (1996).
Molecular-dynamics simulation of domain movements in aspartate aminotransferase.
  Eur J Biochem, 240, 751-755.  
8855356 S.Vaccari, S.Benci, A.Peracchi, and A.Mozzarelli (1996).
Time-resolved fluorescence of tryptophan synthase.
  Biophys Chem, 61, 9.  
8665890 Z.Marković-Housley, T.Schirmer, E.Hohenester, A.R.Khomutov, R.M.Khomutov, M.Y.Karpeisky, E.Sandmeier, P.Christen, and J.N.Jansonius (1996).
Crystal structures and solution studies of oxime adducts of mitochondrial aspartate aminotransferase.
  Eur J Biochem, 236, 1025-1032.
PDB codes: 1oxo 1oxp
  8528073 J.J.Onuffer, and J.F.Kirsch (1995).
Redesign of the substrate specificity of Escherichia coli aspartate aminotransferase to that of Escherichia coli tyrosine aminotransferase by homology modeling and site-directed mutagenesis.
  Protein Sci, 4, 1750-1757.  
7588727 L.Birolo, E.Sandmeier, P.Christen, and R.A.John (1995).
The roles of Tyr70 and Tyr225 in aspartate aminotransferase assessed by analysing the effects of mutations on the multiple reactions of the substrate analogue serine o-sulphate.
  Eur J Biochem, 232, 859-864.  
  8563634 M.D.Toney, S.Pascarella, and D.De Biase (1995).
Active site model for gamma-aminobutyrate aminotransferase explains substrate specificity and inhibitor reactivities.
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7780027 W.R.Fiori, and G.L.Millhauser (1995).
Exploring the peptide 3(10)-helix reversible alpha-helix equilibrium with double label electron spin resonance.
  Biopolymers, 37, 243-250.  
8110969 S.E.Huston, and G.R.Marshall (1994).
Alpha/3(10)-helix transitions in alpha-methylalanine homopeptides: conformational transition pathway and potential of mean force.
  Biopolymers, 34, 75-90.  
8404895 A.Garnier, and R.A.John (1993).
Probes of ligand-induced conformational change in aspartate aminotransferase.
  Eur J Biochem, 216, 763-768.  
  8428572 S.Subramaniam, M.Gerstein, D.Oesterhelt, and R.Henderson (1993).
Electron diffraction analysis of structural changes in the photocycle of bacteriorhodopsin.
  EMBO J, 12, 1-8.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.