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PDBsum entry 1asm
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Aminotransferase PDB id
1asm

 

 

 

 

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Contents
Protein chains
396 a.a. *
Ligands
PLP ×2
MAE ×2
Waters ×223
* Residue conservation analysis
PDB id:
1asm
Name: Aminotransferase
Title: Crystal structures of escherichia coli aspartate aminotransferase in two conformations: comparison of an unliganded open and two liganded closed forms
Structure: Aspartate aminotransferase. Chain: a, b. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.35Å     R-factor:   0.188    
Authors: J.Jaeger,J.N.Jansonius
Key ref: J.Jäger et al. (1994). Crystal structures of Escherichia coli aspartate aminotransferase in two conformations. Comparison of an unliganded open and two liganded closed forms. J Mol Biol, 239, 285-305. PubMed id: 8196059
Date:
16-Sep-93     Release date:   31-Jan-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00509  (AAT_ECOLI) -  Aspartate aminotransferase from Escherichia coli (strain K12)
Seq:
Struc: 		396 a.a.
396 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.6.1.1  - aspartate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate
L-aspartate
 +
2-oxoglutarate
Bound ligand (Het Group name = MAE)
matches with 88.89% similarity 		= oxaloacetate
 + L-glutamate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PLP) matches with 93.75% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
J Mol Biol 239:285-305 (1994)
PubMed id: 8196059  
 
 
Crystal structures of Escherichia coli aspartate aminotransferase in two conformations. Comparison of an unliganded open and two liganded closed forms.
J.Jäger, M.Moser, U.Sauder, J.N.Jansonius.
 
  ABSTRACT  
 
Three crystal structures of wild type E. coli aspartate aminotransferase (E.C.2.6.1.1) in space group P2(1) have been determined at resolution limits between 2.6 and 2.35 A. The unliganded enzyme and its complexes with the substrate analogues maleate and 2-methylaspartate resulted in different conformations. The unit cell parameters of the unliganded and the inhibited enzyme are a = 87.2, b = 79.9, c = 89.8 A and beta = 119.1 degrees, and a = 85.4, b = 79.8, c = 89.5 A and beta = 118.6 degrees, respectively. The crystallographic symmetry is pseudo-C222(1). The liganded enzyme structures were solved by difference Fourier techniques from that of a Val39-->Leu mutant partially refined to an R-factor of 0.22 at 2.85 A. They have a "closed" conformation like the chicken mAATase:maleate complex. The models were refined to R-factors of 0.19 (maleate complex) and 0.18 (2-methylaspartate complex) by molecular dynamics and restrained least squares methods. The unliganded crystal form was solved by molecular replacement and refined to an R-factor of 0.19 at 2.5 A resolution. The structure is in a "half-open" conformation, with the small domain rotated about 6 degrees from the closed conformation. The cofactor pyridoxal phosphate has a more relaxed conformation than in mAATase. Both maleate and 2-methylaspartate are hydrogen-bonded to the active site as in mAATase. The C alpha-CH3 bond of 2-methylaspartate is oriented at right angles to the cofactor pyridine ring, the most productive orientation for alpha-deprotonation of the substrate L-aspartate. Comparisons with earlier determined eAATase structures in space group C222(1) revealed differences that can probably be attributed to the somewhat lower resolution of the orthorhombic structures and/or mutations in the eAATases used in those studies. The present P2(1) structures confirm the justification of extrapolating properties of active site point mutants to the vertebrate isozymes. They will serve as reference in the interpretation of the properties of further site-directed mutants in continued studies of structure-function relationships of this enzyme.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21332942 H.J.Wu, Y.Yang, S.Wang, J.Q.Qiao, Y.F.Xia, Y.Wang, W.D.Wang, S.F.Gao, J.Liu, P.Q.Xue, and X.W.Gao (2011).
Cloning, expression and characterization of a new aspartate aminotransferase from Bacillus subtilis B3.
  FEBS J, 278, 1345-1357.  
20977429 Q.Han, H.Robinson, T.Cai, D.A.Tagle, and J.Li (2011).
Biochemical and structural characterization of mouse mitochondrial aspartate aminotransferase, a newly identified kynurenine aminotransferase-IV.
  Biosci Rep, 31, 323-332.
PDB codes: 3pd6 3pdb
19826765 Q.Han, T.Cai, D.A.Tagle, and J.Li (2010).
Structure, expression, and function of kynurenine aminotransferases in human and rodent brains.
  Cell Mol Life Sci, 67, 353-368.
PDB code: 3hlm
19917609 T.Lendrihas, G.A.Hunter, and G.C.Ferreira (2010).
Serine 254 enhances an induced fit mechanism in murine 5-aminolevulinate synthase.
  J Biol Chem, 285, 3351-3359.  
19640845 M.Goto, T.Yamauchi, N.Kamiya, I.Miyahara, T.Yoshimura, H.Mihara, T.Kurihara, K.Hirotsu, and N.Esaki (2009).
Crystal structure of a homolog of mammalian serine racemase from Schizosaccharomyces pombe.
  J Biol Chem, 284, 25944-25952.
PDB codes: 1wtc 2zr8
18831049 T.Tomita, T.Miyagawa, T.Miyazaki, S.Fushinobu, T.Kuzuyama, and M.Nishiyama (2009).
Mechanism for multiple-substrates recognition of alpha-aminoadipate aminotransferase from Thermus thermophilus.
  Proteins, 75, 348-359.
PDB codes: 2zp7 3cbf
18922152 J.M.Thornburg, K.K.Nelson, B.F.Clem, A.N.Lane, S.Arumugam, A.Simmons, J.W.Eaton, S.Telang, and J.Chesney (2008).
Targeting aspartate aminotransferase in breast cancer.
  Breast Cancer Res, 10, R84.  
18056995 Q.Han, H.Robinson, and J.Li (2008).
Crystal Structure of Human Kynurenine Aminotransferase II.
  J Biol Chem, 283, 3567-3573.
PDB codes: 2qlr 2r2n
18620547 Q.Han, T.Cai, D.A.Tagle, H.Robinson, and J.Li (2008).
Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II.
  Biosci Rep, 28, 205-215.
PDB code: 3dc1
18186649 Q.Han, Y.G.Gao, H.Robinson, and J.Li (2008).
Structural insight into the mechanism of substrate specificity of aedes kynurenine aminotransferase.
  Biochemistry, 47, 1622-1630.
PDB codes: 2r5c 2r5e
18366019 R.Z.Liao, W.J.Ding, J.G.Yu, W.H.Fang, and R.Z.Liu (2008).
Theoretical studies on pyridoxal 5'-phosphate-dependent transamination of alpha-amino acids.
  J Comput Chem, 29, 1919-1929.  
17300176 S.Lima, R.Khristoforov, C.Momany, and R.S.Phillips (2007).
Crystal structure of Homo sapiens kynureninase.
  Biochemistry, 46, 2735-2744.
PDB code: 2hzp
17050531 N.H.Yennawar, M.M.Islam, M.Conway, R.Wallin, and S.M.Hutson (2006).
Human mitochondrial branched chain aminotransferase isozyme: structural role of the CXXC center in catalysis.
  J Biol Chem, 281, 39660-39671.
PDB codes: 2hdk 2hg8 2hgw 2hgx 2hhf
15889412 K.Hirotsu, M.Goto, A.Okamoto, and I.Miyahara (2005).
Dual substrate recognition of aminotransferases.
  Chem Rec, 5, 160-172.  
14761974 M.Goto, R.Omi, I.Miyahara, A.Hosono, H.Mizuguchi, H.Hayashi, H.Kagamiyama, and K.Hirotsu (2004).
Crystal structures of glutamine:phenylpyruvate aminotransferase from Thermus thermophilus HB8: induced fit and substrate recognition.
  J Biol Chem, 279, 16518-16525.
PDB codes: 1v2d 1v2e 1v2f
14767072 S.C.Rothman, M.Voorhies, and J.F.Kirsch (2004).
Directed evolution relieves product inhibition and confers in vivo function to a rationally designed tyrosine aminotransferase.
  Protein Sci, 13, 763-772.  
15103612 Y.Katsura, M.Shirouzu, H.Yamaguchi, R.Ishitani, O.Nureki, S.Kuramitsu, H.Hayashi, and S.Yokoyama (2004).
Crystal structure of a putative aspartate aminotransferase belonging to subgroup IV.
  Proteins, 55, 487-492.
PDB code: 1iug
12488449 H.Hayashi, H.Mizuguchi, I.Miyahara, Y.Nakajima, K.Hirotsu, and H.Kagamiyama (2003).
Conformational change in aspartate aminotransferase on substrate binding induces strain in the catalytic group and enhances catalysis.
  J Biol Chem, 278, 9481-9488.
PDB codes: 1ix6 1ix7 1ix8
12723595 H.Kim, K.Ikegami, M.Nakaoka, M.Yagi, H.Shibata, and Y.Sawa (2003).
Characterization of aspartate aminotransferase from the cyanobacterium Phormidium lapideum.
  Biosci Biotechnol Biochem, 67, 490-498.  
  16233433 H.Kim, M.Nakaoka, M.Yagi, H.Ashida, K.Hamada, H.Shibata, and Y.Sawa (2003).
Cloning, structural analysis and expression of the gene encoding aspartate aminotransferase from the thermophilic cyanobacterium Phormidium lapideum.
  J Biosci Bioeng, 95, 421-424.  
12595727 J.K.Yang, C.Chang, S.J.Cho, J.Y.Lee, Y.G.Yu, S.H.Eom, and S.W.Suh (2003).
Crystallization and preliminary X-ray analysis of the Mj0684 gene product, a putative aspartate aminotransferase, from Methanococcus jannaschii.
  Acta Crystallogr D Biol Crystallogr, 59, 563-565.  
12952961 R.Omi, M.Goto, I.Miyahara, H.Mizuguchi, H.Hayashi, H.Kagamiyama, and K.Hirotsu (2003).
Crystal structures of threonine synthase from Thermus thermophilus HB8: conformational change, substrate recognition, and mechanism.
  J Biol Chem, 278, 46035-46045.
PDB codes: 1uim 1uin 1uiq 1v7c
11967363 E.Deu, K.A.Koch, and J.F.Kirsch (2002).
The role of the conserved Lys68*:Glu265 intersubunit salt bridge in aspartate aminotransferase kinetics: multiple forced covariant amino acid substitutions in natural variants.
  Protein Sci, 11, 1062-1073.  
12191993 J.Zhang, and G.C.Ferreira (2002).
Transient state kinetic investigation of 5-aminolevulinate synthase reaction mechanism.
  J Biol Chem, 277, 44660-44669.  
11875074 L.Birolo, F.Dal Piaz, P.Pucci, and G.Marino (2002).
Structural characterization of the M* partly folded intermediate of wild type and P138A aspartate aminotransferase from Escherichia coli.
  J Biol Chem, 277, 17428-17437.  
12146963 O.Hur, D.Niks, P.Casino, and M.F.Dunn (2002).
Proton transfers in the beta-reaction catalyzed by tryptophan synthase.
  Biochemistry, 41, 9991.  
11877399 V.Trivedi, A.Gupta, V.R.Jala, P.Saravanan, G.S.Rao, N.A.Rao, H.S.Savithri, and H.S.Subramanya (2002).
Crystal structure of binary and ternary complexes of serine hydroxymethyltransferase from Bacillus stearothermophilus: insights into the catalytic mechanism.
  J Biol Chem, 277, 17161-17169.
PDB codes: 1kkj 1kkp 1kl1 1kl2
11248682 A.Matharu, H.Hayashi, H.Kagamiyama, B.Maras, and R.A.John (2001).
Contributions of the substrate-binding arginine residues to maleate-induced closure of the active site of Escherichia coli aspartate aminotransferase.
  Eur J Biochem, 268, 1640-1645.  
11933245 H.Kagamiyama, and H.Hayashi (2001).
Release of enzyme strain during catalysis reduces the activation energy barrier.
  Chem Rec, 1, 385-394.  
11294630 K.Haruyama, T.Nakai, I.Miyahara, K.Hirotsu, H.Mizuguchi, H.Hayashi, and H.Kagamiyama (2001).
Structures of Escherichia coli histidinol-phosphate aminotransferase and its complexes with histidinol-phosphate and N-(5'-phosphopyridoxyl)-L-glutamate: double substrate recognition of the enzyme.
  Biochemistry, 40, 4633-4644.
PDB codes: 1gew 1gex 1gey
11264579 N.Yennawar, J.Dunbar, M.Conway, S.Hutson, and G.Farber (2001).
The structure of human mitochondrial branched-chain aminotransferase.
  Acta Crystallogr D Biol Crystallogr, 57, 506-515.
PDB codes: 1ekf 1ekp 1ekv
11737206 R.Contestabile, A.Paiardini, S.Pascarella, M.L.di Salvo, S.D'Aguanno, and F.Bossa (2001).
l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions.
  Eur J Biochem, 268, 6508-6525.  
10673430 G.Schneider, H.Käck, and Y.Lindqvist (2000).
The manifold of vitamin B6 dependent enzymes.
  Structure, 8, R1-R6.  
10858450 J.Ishijima, T.Nakai, S.Kawaguchi, K.Hirotsu, and S.Kuramitsu (2000).
Free energy requirement for domain movement of an enzyme.
  J Biol Chem, 275, 18939-18945.
PDB codes: 1c9c 1cq6 1cq7 1cq8
10785402 L.Birolo, M.L.Tutino, B.Fontanella, C.Gerday, K.Mainolfi, S.Pascarella, G.Sannia, F.Vinci, and G.Marino (2000).
Aspartate aminotransferase from the Antarctic bacterium Pseudoalteromonas haloplanktis TAC 125. Cloning, expression, properties, and molecular modelling.
  Eur J Biochem, 267, 2790-2802.  
9880502 B.Mouratou, P.Kasper, H.Gehring, and P.Christen (1999).
Conversion of tyrosine phenol-lyase to dicarboxylic amino acid beta-lyase, an enzyme not found in nature.
  J Biol Chem, 274, 1320-1325.  
10212188 G.A.Hunter, and G.C.Ferreira (1999).
Pre-steady-state reaction of 5-aminolevulinate synthase. Evidence for a rate-determining product release.
  J Biol Chem, 274, 12222-12228.  
10223296 K.A.Denessiouk, A.I.Denesyuk, J.V.Lehtonen, T.Korpela, and M.S.Johnson (1999).
Common structural elements in the architecture of the cofactor-binding domains in unrelated families of pyridoxal phosphate-dependent enzymes.
  Proteins, 35, 250-261.  
10531314 R.Graber, P.Kasper, V.N.Malashkevich, P.Strop, H.Gehring, J.N.Jansonius, and P.Christen (1999).
Conversion of aspartate aminotransferase into an L-aspartate beta-decarboxylase by a triple active-site mutation.
  J Biol Chem, 274, 31203-31208.  
9891001 S.Oue, A.Okamoto, T.Yano, and H.Kagamiyama (1999).
Redesigning the substrate specificity of an enzyme by cumulative effects of the mutations of non-active site residues.
  J Biol Chem, 274, 2344-2349.
PDB code: 1yoo
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.  
  9655342 C.J.Jeffery, T.Barry, S.Doonan, G.A.Petsko, and D.Ringe (1998).
Crystal structure of Saccharomyces cerevisiae cytosolic aspartate aminotransferase.
  Protein Sci, 7, 1380-1387.
PDB code: 1yaa
9538014 D.Peisach, D.M.Chipman, P.W.Van Ophem, J.M.Manning, and D.Ringe (1998).
Crystallographic study of steps along the reaction pathway of D-amino acid aminotransferase.
  Biochemistry, 37, 4958-4967.
PDB codes: 3daa 4daa
9562556 D.T.Gallagher, G.L.Gilliland, G.Xiao, J.Zondlo, K.E.Fisher, D.Chinchilla, and E.Eisenstein (1998).
Structure and control of pyridoxal phosphate dependent allosteric threonine deaminase.
  Structure, 6, 465-475.
PDB code: 1tdj
9671513 G.F.Stamper, A.A.Morollo, D.Ringe, and C.G.Stamper (1998).
Reaction of alanine racemase with 1-aminoethylphosphonic acid forms a stable external aldimine.
  Biochemistry, 37, 10438-10445.
PDB code: 1bd0
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.  
9201992 A.Artigues, A.Iriarte, and M.Martinez-Carrion (1997).
Refolding intermediates of acid-unfolded mitochondrial aspartate aminotransferase bind to hsp70.
  J Biol Chem, 272, 16852-16861.  
9414203 D.M.van Aalten, D.A.Conn, B.L.de Groot, H.J.Berendsen, J.B.Findlay, and A.Amadei (1997).
Protein dynamics derived from clusters of crystal structures.
  Biophys J, 73, 2891-2896.  
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.  
9083108 M.Bergdoll, M.H.Remy, C.Cagnon, J.M.Masson, and P.Dumas (1997).
Proline-dependent oligomerization with arm exchange.
  Structure, 5, 391-401.  
9268327 R.A.Vacca, S.Giannattasio, R.Graber, E.Sandmeier, E.Marra, and P.Christen (1997).
Active-site Arg --> Lys substitutions alter reaction and substrate specificity of aspartate aminotransferase.
  J Biol Chem, 272, 21932-21937.  
8611515 J.M.Goldberg, and J.F.Kirsch (1996).
The reaction catalyzed by Escherichia coli aspartate aminotransferase has multiple partially rate-determining steps, while that catalyzed by the Y225F mutant is dominated by ketimine hydrolysis.
  Biochemistry, 35, 5280-5291.  
8855356 S.Vaccari, S.Benci, A.Peracchi, and A.Mozzarelli (1996).
Time-resolved fluorescence of tryptophan synthase.
  Biophys Chem, 61, 9.  
7744078 H.Chen, P.Gollnick, and R.S.Phillips (1995).
Site-directed mutagenesis of His343-->Ala in Citrobacter freundii tyrosine phenol-lyase. Effects on the kinetic mechanism and rate-determining step.
  Eur J Biochem, 229, 540-549.  
  8528072 J.J.Onuffer, B.T.Ton, I.Klement, and J.F.Kirsch (1995).
The use of natural and unnatural amino acid substrates to define the substrate specificity differences of Escherichia coli aspartate and tyrosine aminotransferases.
  Protein Sci, 4, 1743-1749.  
  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.
  Protein Sci, 4, 2366-2374.  
7851426 R.A.Vacca, P.Christen, V.N.Malashkevich, J.N.Jansonius, and E.Sandmeier (1995).
Substitution of apolar residues in the active site of aspartate aminotransferase by histidine. Effects on reaction and substrate specificity.
  Eur J Biochem, 227, 481-487.
PDB code: 1ari
7493966 R.Buchli, D.Alberati-Giani, P.Malherbe, C.Köhler, C.Broger, and A.M.Cesura (1995).
Cloning and functional expression of a soluble form of kynurenine/alpha-aminoadipate aminotransferase from rat kidney.
  J Biol Chem, 270, 29330-29335.  
7556224 R.Graber, P.Kasper, V.N.Malashkevich, E.Sandmeier, P.Berger, H.Gehring, J.N.Jansonius, and P.Christen (1995).
Changing the reaction specificity of a pyridoxal-5'-phosphate-dependent enzyme.
  Eur J Biochem, 232, 686-690.
PDB codes: 1arg 1arh
7664122 V.N.Malashkevich, J.J.Onuffer, J.F.Kirsch, and J.N.Jansonius (1995).
Alternating arginine-modulated substrate specificity in an engineered tyrosine aminotransferase.
  Nat Struct Biol, 2, 548-553.
PDB codes: 1ahe 1ahf 1ahg 1ahx 1ahy
7735837 X.Wu, B.Knudsen, S.M.Feller, J.Zheng, A.Sali, D.Cowburn, H.Hanafusa, and J.Kuriyan (1995).
Structural basis for the specific interaction of lysine-containing proline-rich peptides with the N-terminal SH3 domain of c-Crk.
  Structure, 3, 215-226.
PDB codes: 1cka 1ckb
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.

 

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