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PDBsum entry 1h0c
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Transferase PDB id
1h0c

 

 

 

 

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Contents
Protein chain
386 a.a. *
Ligands
PLP
AOA
GOL ×6
Waters ×143
* Residue conservation analysis
PDB id:
1h0c
Name: Transferase
Title: The crystal structure of human alanine:glyoxylate aminotransferase
Structure: Serine--glyoxylate aminotransferase. Chain: a. Synonym: agt, spt, alanine--glyoxylate aminotransferase. Engineered: yes. Other_details: lysine - pyridoxal phosphate at a 209
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PDB file)
Resolution:
2.50Å     R-factor:   0.231     R-free:   0.286
Authors: X.Zhang,C.J.Danpure,S.M.Roe,L.H.Pearl
Key ref:
X.Zhang et al. (2003). Crystal structure of alanine:glyoxylate aminotransferase and the relationship between genotype and enzymatic phenotype in primary hyperoxaluria type 1. J Mol Biol, 331, 643-652. PubMed id: 12899834 DOI: 10.1016/S0022-2836(03)00791-5
Date:
17-Jun-02     Release date:   12-Jun-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P21549  (SPYA_HUMAN) -  Alanine--glyoxylate aminotransferase from Homo sapiens
Seq:
Struc: 		392 a.a.
386 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.2.6.1.44  - alanine--glyoxylate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: glyoxylate + L-alanine = glycine + pyruvate
glyoxylate
Bound ligand (Het Group name = AOA)
matches with 83.33% similarity 		+ L-alanine
 = glycine
 + pyruvate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PLP) matches with 93.75% similarity
   Enzyme class 2: E.C.2.6.1.51  - serine--pyruvate transaminase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-serine + pyruvate = 3-hydroxypyruvate + L-alanine
L-serine
 +
pyruvate
Bound ligand (Het Group name = AOA)
matches with 71.43% similarity 		=
3-hydroxypyruvate
Bound ligand (Het Group name = GOL)
matches with 85.71% similarity 		+ L-alanine
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PLP) matches with 93.75% similarity
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

 

 
    reference    
 
 
DOI no: 10.1016/S0022-2836(03)00791-5 J Mol Biol 331:643-652 (2003)
PubMed id: 12899834  
 
 
Crystal structure of alanine:glyoxylate aminotransferase and the relationship between genotype and enzymatic phenotype in primary hyperoxaluria type 1.
X.Zhang, S.M.Roe, Y.Hou, M.Bartlam, Z.Rao, L.H.Pearl, C.J.Danpure.
 
  ABSTRACT  
 
A deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase (AGT) is responsible for the potentially lethal hereditary kidney stone disease primary hyperoxaluria type 1 (PH1). Many of the mutations in the gene encoding AGT are associated with specific enzymatic phenotypes such as accelerated proteolysis (Ser205Pro), intra-peroxisomal aggregation (Gly41Arg), inhibition of pyridoxal phosphate binding and loss of catalytic activity (Gly82Glu), and peroxisome-to-mitochondrion mistargeting (Gly170Arg). Several mutations, including that responsible for AGT mistargeting, co-segregate and interact synergistically with a Pro11Leu polymorphism found at high frequency in the normal population. In order to gain further insights into the mechanistic link between genotype and enzymatic phenotype in PH1, we have determined the crystal structure of normal human AGT complexed to the competitive inhibitor amino-oxyacetic acid to 2.5A. Analysis of this structure allows the effects of these mutations and polymorphism to be rationalised in terms of AGT tertiary and quaternary conformation, and in particular it provides a possible explanation for the Pro11Leu-Gly170Arg synergism that leads to AGT mistargeting.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Overall topology of the normal AGT dimer. (A) and (B) The a-chain is colour-coded as follows: magenta, extended N-terminal segment; red, large N-terminal domain; green, small C-terminal domain. The b-chain is colour coded as follows: cyan, extended N-terminal segment; yellow, large N-terminal domain; blue, small C-terminal domain. B is rotated 180° in the horizontal plane relative to A. Residues 41, 82, 170, 205, 209, and 244 are indicated on the a-chain, residue 11 is indicated on the b-chain. (C) Stereo pair of C^a chain, same orientation as A. The pyridoxal phosphate cofactor is in shown in red and the amino-oxyacetic acid inhibitor is shown in orange. The N and C-terminal residues identified in the structure (4 and 390, respectively) and every other 50 residues are numbered on the a-chain (green). 		Figure 3.
Figure 3. Active site and dimerisation interface of normal AGT. (A) Active site of AGT. AOA, amino-oxyacetic acid; Lys209a is coloured magenta, the a-chain green, and the b-chain blue. For PLP and AOA, the carbon atoms are in yellow, oxygen atoms in red, phosphorous atom in orange, and nitrogen atoms in blue. Key residues are labelled and important hydrogen bonds discussed in the text are represented by dotted lines. (B) Locations of Gly41 and Gly42 at the dimerisation interface. The a-chain is coloured green, and the b-chain blue.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 331, 643-652) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20056599 A.Albert, C.Yunta, R.Arranz, A.Peña, E.Salido, J.M.Valpuesta, and J.Martín-Benito (2010).
Structure of GroEL in complex with an early folding intermediate of alanine glyoxylate aminotransferase.
  J Biol Chem, 285, 6371-6376.  
20133649 B.Cellini, R.Montioli, A.Paiardini, A.Lorenzetto, F.Maset, T.Bellini, E.Oppici, and C.B.Voltattorni (2010).
Molecular defects of the glycine 41 variants of alanine glyoxylate aminotransferase associated with primary hyperoxaluria type I.
  Proc Natl Acad Sci U S A, 107, 2896-2901.  
20852637 I.Ramazzina, R.Costa, L.Cendron, R.Berni, A.Peracchi, G.Zanotti, and R.Percudani (2010).
An aminotransferase branch point connects purine catabolism to amino acid recycling.
  Nat Chem Biol, 6, 801-806.  
20018850 R.N.Rodionov, D.J.Murry, S.F.Vaulman, J.W.Stevens, and S.R.Lentz (2010).
Human alanine-glyoxylate aminotransferase 2 lowers asymmetric dimethylarginine and protects from inhibition of nitric oxide production.
  J Biol Chem, 285, 5385-5391.  
19155213 B.Cellini, R.Montioli, A.Paiardini, A.Lorenzetto, and C.B.Voltattorni (2009).
Molecular Insight into the Synergism between the Minor Allele of Human Liver Peroxisomal Alanine:Glyoxylate Aminotransferase and the F152I Mutation.
  J Biol Chem, 284, 8349-8358.  
19225556 B.Hoppe, B.B.Beck, and D.S.Milliner (2009).
The primary hyperoxalurias.
  Kidney Int, 75, 1264-1271.  
19479957 E.L.Williams, C.Acquaviva, A.Amoroso, F.Chevalier, M.Coulter-Mackie, C.G.Monico, D.Giachino, T.Owen, A.Robbiano, E.Salido, H.Waterham, and G.Rumsby (2009).
Primary hyperoxaluria type 1: update and additional mutation analysis of the AGXT gene.
  Hum Mutat, 30, 910-917.  
19545238 S.Donini, M.Ferrari, C.Fedeli, M.Faini, I.Lamberto, A.S.Marletta, L.Mellini, M.Panini, R.Percudani, L.Pollegioni, L.Caldinelli, S.Petrucco, and A.Peracchi (2009).
Recombinant production of eight human cytosolic aminotransferases and assessment of their potential involvement in glyoxylate metabolism.
  Biochem J, 422, 265-272.  
18782763 E.D.Hopper, A.M.Pittman, M.C.Fitzgerald, and C.L.Tucker (2008).
In Vivo and in Vitro Examination of Stability of Primary Hyperoxaluria-associated Human Alanine:Glyoxylate Aminotransferase.
  J Biol Chem, 283, 30493-30502.  
18950711 F.Rossi, R.Schwarcz, and M.Rizzi (2008).
Curiosity to kill the KAT (kynurenine aminotransferase): structural insights into brain kynurenic acid synthesis.
  Curr Opin Struct Biol, 18, 748-755.  
19026355 G.Rumsby (2008).
Oxalate transport as contributor to primary hyperoxaluria: the jury is still out.
  Am J Kidney Dis, 52, 1031-1034.  
18560158 H.Sakuraba, K.Yoneda, K.Takeuchi, H.Tsuge, N.Katunuma, and T.Ohshima (2008).
Structure of an archaeal alanine:glyoxylate aminotransferase.
  Acta Crystallogr D Biol Crystallogr, 64, 696-699.
PDB code: 2zc0
18175955 M.Ikeda, H.Kanouchi, and Y.Minatogawa (2008).
Characterization of peroxisomal targeting signals on alanine: glyoxylate aminotransferase.
  Biol Pharm Bull, 31, 131-134.  
17989071 Y.Yoshikane, N.Yokochi, M.Yamasaki, K.Mizutani, K.Ohnishi, B.Mikami, H.Hayashi, and T.Yagi (2008).
Crystal structure of pyridoxamine-pyruvate aminotransferase from Mesorhizobium loti MAFF303099.
  J Biol Chem, 283, 1120-1127.
PDB codes: 2z9u 2z9v 2z9w 2z9x
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
17020415 A.E.Bobrowski, and C.B.Langman (2006).
Hyperoxaluria and systemic oxalosis: current therapy and future directions.
  Expert Opin Pharmacother, 7, 1887-1896.  
16988727 D.Milliner (2006).
Treatment of the primary hyperoxalurias: a new chapter.
  Kidney Int, 70, 1198-1200.  
16585514 F.Rossi, S.Garavaglia, G.B.Giovenzana, B.Arcà, J.Li, and M.Rizzi (2006).
Crystal structure of the Anopheles gambiae 3-hydroxykynurenine transaminase.
  Proc Natl Acad Sci U S A, 103, 5711-5716.
PDB codes: 2ch1 2ch2
16990263 Q.Han, H.Robinson, Y.G.Gao, N.Vogelaar, S.R.Wilson, M.Rizzi, and J.Li (2006).
Crystal structures of Aedes aegypti alanine glyoxylate aminotransferase.
  J Biol Chem, 281, 37175-37182.
PDB codes: 2huf 2hui 2huu
15772831 E.Leumann, and B.Hoppe (2005).
Primary hyperoxaluria type 1: is genotyping clinically helpful?
  Pediatr Nephrol, 20, 555-557.  
15657930 G.W.Han, R.Schwarzenbacher, R.Page, L.Jaroszewski, P.Abdubek, E.Ambing, T.Biorac, J.M.Canaves, H.J.Chiu, X.Dai, A.M.Deacon, M.DiDonato, M.A.Elsliger, A.Godzik, C.Grittini, S.K.Grzechnik, J.Hale, E.Hampton, J.Haugen, M.Hornsby, H.E.Klock, E.Koesema, A.Kreusch, P.Kuhn, S.A.Lesley, I.Levin, D.McMullan, T.M.McPhillips, M.D.Miller, A.Morse, K.Moy, E.Nigoghossian, J.Ouyang, J.Paulsen, K.Quijano, R.Reyes, E.Sims, G.Spraggon, R.C.Stevens, H.van den Bedem, J.Velasquez, J.Vincent, F.von Delft, X.Wang, B.West, A.White, G.Wolf, Q.Xu, O.Zagnitko, K.O.Hodgson, J.Wooley, and I.A.Wilson (2005).
Crystal structure of an alanine-glyoxylate aminotransferase from Anabaena sp. at 1.70 A resolution reveals a noncovalently linked PLP cofactor.
  Proteins, 58, 971-975.
PDB code: 1vjo
15911627 P.A.Huber, G.M.Birdsey, M.J.Lumb, D.T.Prowse, T.J.Perkins, D.R.Knight, and C.J.Danpure (2005).
Peroxisomal import of human alanine:glyoxylate aminotransferase requires ancillary targeting information remote from its C terminus.
  J Biol Chem, 280, 27111-27120.  
15849465 S.Koul, T.Johnson, S.Pramanik, and H.Koul (2005).
Cellular transfection to deliver alanine-glyoxylate aminotransferase to hepatocytes: a rational gene therapy for primary hyperoxaluria-1 (PH-1).
  Am J Nephrol, 25, 176-182.  
15021200 C.B.Langman (2004).
The molecular basis of kidney stones.
  Curr Opin Pediatr, 16, 188-193.  
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 code is shown on the right.

 

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