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protein ligands metals Protein-protein interface(s) links
Ligase PDB id
3bg5
Jmol
Contents
Protein chains
1137 a.a. *
1074 a.a. *
Ligands
BTI ×4
PYR ×4
ATP ×2
Metals
_MN ×4
* Residue conservation analysis
PDB id:
3bg5
Name: Ligase
Title: Crystal structure of staphylococcus aureus pyruvate carboxylase
Structure: Pyruvate carboxylase. Chain: a, b, c, d. Engineered: yes
Source: Staphylococcus aureus. Organism_taxid: 1280. Gene: pyca. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.80Å     R-factor:   0.217     R-free:   0.268
Authors: S.Xiang,L.Tong
Key ref:
S.Xiang and L.Tong (2008). Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction. Nat Struct Mol Biol, 15, 295-302. PubMed id: 18297087 DOI: 10.1038/nsmb.1393
Date:
26-Nov-07     Release date:   26-Feb-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q99UY8  (Q99UY8_STAAM) -  Pyruvate carboxylase
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1150 a.a.
1137 a.a.
Protein chains
Pfam   ArchSchema ?
Q99UY8  (Q99UY8_STAAM) -  Pyruvate carboxylase
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1150 a.a.
1074 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     metabolic process   2 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
DOI no: 10.1038/nsmb.1393 Nat Struct Mol Biol 15:295-302 (2008)
PubMed id: 18297087  
 
 
Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction.
S.Xiang, L.Tong.
 
  ABSTRACT  
 
Pyruvate carboxylase (PC) catalyzes the biotin-dependent production of oxaloacetate and has important roles in gluconeogenesis, lipogenesis, insulin secretion and other cellular processes. PC contains the biotin carboxylase (BC), carboxyltransferase (CT) and biotin-carboxyl carrier protein (BCCP) domains. We report here the crystal structures at 2.8-A resolution of full-length PC from Staphylococcus aureus and the C-terminal region (missing only the BC domain) of human PC. A conserved tetrameric association is observed for both enzymes, and our structural and mutagenesis studies reveal a previously uncharacterized domain, the PC tetramerization (PT) domain, which is important for oligomerization. A BCCP domain is located in the active site of the CT domain, providing the first molecular insights into how biotin participates in the carboxyltransfer reaction. There are dramatic differences in domain positions in the monomer and the organization of the tetramer between these enzymes and the PC from Rhizobium etli.
 
  Selected figure(s)  
 
Figure 1.
(a) Domain organization of human PC. BC, biotin carboxylase (red); CT, carboxyltransferase (green); PT, PC tetramerization (gold), which was identified from our studies; BCCP, biotin-carboxyl carrier protein (blue). (b) Schematic drawing of the structure of the CT+PT+BCCP domain tetramer of human PC. The domains in monomer 1 are given separate colors as in panel a, whereas the other three monomers are colored magenta, cyan and yellow. The biotin moiety on the BCCP molecule in blue is shown in black, pointed into the active site of CT. (c) Detailed interactions between the PT domains of monomers 1 and 3 in the tetramer interface of human PC. (d) Crystal structure of the dimer of the F1077A mutant of the CT+PT+BCCP domain of human PC. The mutation has disrupted the tetramer. All the structure figures were produced with Pymol^30. 		Figure 3.
(a) Schematic drawing of the tetramer of the carboxyltransferase and PC tetramerization (CT+PT) domain of human and S. aureus PC, viewed in the same orientation. (b) Schematic drawing of the four CT+PT domains in the R. etli tetramer^19, viewed in the same orientation as in panel a for the two monomers in green and yellow. (c) Overlay of the structures of monomer 1 in S. aureus PC (colored) and the monomer bound to ethyl-CoA (black) or the free monomer (gray) of R. etli PC^19.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2008, 15, 295-302) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21426897 A.Adina-Zada, R.Hazra, C.Sereeruk, S.Jitrapakdee, T.N.Zeczycki, M.S.Maurice, W.W.Cleland, J.C.Wallace, and P.V.Attwood (2011).
Probing the allosteric activation of pyruvate carboxylase using 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate as a fluorescent mimic of the allosteric activator acetyl CoA.
  Arch Biochem Biophys, 509, 117-126.  
21204864 G.Gago, L.Diacovich, A.Arabolaza, S.C.Tsai, and H.Gramajo (2011).
Fatty acid biosynthesis in actinomycetes.
  FEMS Microbiol Rev, 35, 475-497.  
20725044 C.S.Huang, K.Sadre-Bazzaz, Y.Shen, B.Deng, Z.H.Zhou, and L.Tong (2010).
Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase.
  Nature, 466, 1001-1005.
PDB code: 3n6r
20552640 J.C.Wallace (2010).
My favorite pyruvate carboxylase.
  IUBMB Life, 62, 535-538.  
20230056 S.Duangpan, S.Jitrapakdee, A.Adina-Zada, L.Byrne, T.N.Zeczycki, M.St Maurice, W.W.Cleland, J.C.Wallace, and P.V.Attwood (2010).
Probing the catalytic roles of Arg548 and Gln552 in the carboxyl transferase domain of the Rhizobium etli pyruvate carboxylase by site-directed mutagenesis.
  Biochemistry, 49, 3296-3304.  
19213731 C.Y.Chou, L.P.Yu, and L.Tong (2009).
Crystal structure of biotin carboxylase in complex with substrates and implications for its catalytic mechanism.
  J Biol Chem, 284, 11690-11697.
PDB codes: 3g8c 3g8d
19523900 L.P.Yu, S.Xiang, G.Lasso, D.Gil, M.Valle, and L.Tong (2009).
A symmetrical tetramer for S. aureus pyruvate carboxylase in complex with coenzyme A.
  Structure, 17, 823-832.
PDB codes: 3hb9 3hbl 3ho8
19341298 T.N.Zeczycki, M.St Maurice, S.Jitrapakdee, J.C.Wallace, P.V.Attwood, and W.W.Cleland (2009).
Insight into the carboxyl transferase domain mechanism of pyruvate carboxylase from Rhizobium etli.
  Biochemistry, 48, 4305-4313.  
  18540065 N.R.Pendini, S.W.Polyak, G.W.Booker, J.C.Wallace, and M.C.Wilce (2008).
Purification, crystallization and preliminary crystallographic analysis of biotin protein ligase from Staphylococcus aureus.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 520-523.  
18613815 S.Jitrapakdee, M.St Maurice, I.Rayment, W.W.Cleland, J.C.Wallace, and P.V.Attwood (2008).
Structure, mechanism and regulation of pyruvate carboxylase.
  Biochem J, 413, 369-387.  
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.