spacer
spacer
Go to PDB code: 
protein ligands Protein-protein interface(s) links
Transferase PDB id
1fvo
Jmol
Contents
Protein chains
321 a.a. *
Ligands
_CP ×2
Waters ×43
* Residue conservation analysis
PDB id:
1fvo
Name: Transferase
Title: Crystal structure of human ornithine transcarbamylase comple carbamoyl phosphate
Structure: Ornithine transcarbamylase. Chain: a, b. Synonym: otcase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PDB file)
Resolution:
2.60Å     R-factor:   0.202     R-free:   0.236
Authors: D.Shi,H.Morizono,X.Yu,N.M.Allewell,M.Tuchman
Key ref: D.Shi et al. (2001). Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes. Biochem J, 354, 501-509. PubMed id: 11237854 DOI: 10.1042/0264-6021:3540501
Date:
20-Sep-00     Release date:   04-Apr-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00480  (OTC_HUMAN) -  Ornithine carbamoyltransferase, mitochondrial
Seq:
Struc: 		354 a.a.
322 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.1.3.3  - Ornithine carbamoyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Urea Cycle and Arginine Biosynthesis
      Reaction: Carbamoyl phosphate + L-ornithine = phosphate + L-citrulline
Carbamoyl phosphate
Bound ligand (Het Group name = CP)
corresponds exactly 		+ L-ornithine
 = phosphate
 + L-citrulline
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   5 terms 
  Biological process     response to biotin   16 terms 
  Biochemical function     transferase activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1042/0264-6021:3540501 Biochem J 354:501-509 (2001)
PubMed id: 11237854  
 
 
Human ornithine transcarbamylase: crystallographic insights into substrate recognition and conformational changes.
D.Shi, H.Morizono, X.Yu, L.Tong, N.M.Allewell, M.Tuchman.
 
  ABSTRACT  
 
Two crystal structures of human ornithine transcarbamylase (OTCase) complexed with the substrate carbamoyl phosphate (CP) have been solved. One structure, whose crystals were prepared by substituting N-phosphonacetyl-L-ornithine (PALO) liganded crystals with CP, has been refined at 2.4 A (1 A=0.1 nm) resolution to a crystallographic R factor of 18.4%. The second structure, whose crystals were prepared by co-crystallization with CP, has been refined at 2.6 A resolution to a crystallographic R factor of 20.2%. These structures provide important new insights into substrate recognition and ligand-induced conformational changes. Comparison of these structures with the structures of OTCase complexed with the bisubstrate analogue PALO or CP and L-norvaline reveals that binding of the first substrate, CP, induces a global conformational change involving relative domain movement, whereas the binding of the second substrate brings the flexible SMG loop, which is equivalent to the 240s loop in aspartate transcarbamylase, into the active site. The model reveals structural features that define the substrate specificity of the enzyme and that regulate the order of binding and release of products.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19318352 W.Yu, Y.Lin, J.Yao, W.Huang, Q.Lei, Y.Xiong, S.Zhao, and K.L.Guan (2009).
Lysine 88 acetylation negatively regulates ornithine carbamoyltransferase activity in response to nutrient signals.
  J Biol Chem, 284, 13669-13675.  
18971327 Q.Wang, J.Xia, V.Guallar, G.Krilov, and E.R.Kantrowitz (2008).
Mechanism of thermal decomposition of carbamoyl phosphate and its stabilization by aspartate and ornithine transcarbamoylases.
  Proc Natl Acad Sci U S A, 105, 16918-16923.  
17600144 D.Shi, X.Yu, J.Cabrera-Luque, T.Y.Chen, L.Roth, H.Morizono, N.M.Allewell, and M.Tuchman (2007).
A single mutation in the active site swaps the substrate specificity of N-acetyl-L-ornithine transcarbamylase and N-succinyl-L-ornithine transcarbamylase.
  Protein Sci, 16, 1689-1699.
PDB codes: 2g65 2g68 2g6a 2g6c 2g7m 3l02 3l04 3l05 3l06
17334707 J.A.Arranz, E.Riudor, C.Marco-Marín, and V.Rubio (2007).
Estimation of the total number of disease-causing mutations in ornithine transcarbamylase (OTC) deficiency. Value of the OTC structure in predicting a mutation pathogenic potential.
  J Inherit Metab Dis, 30, 217-226.  
17028272 J.L.Llácer, L.M.Polo, S.Tavárez, B.Alarcón, R.Hilario, and V.Rubio (2007).
The gene cluster for agmatine catabolism of Enterococcus faecalis: study of recombinant putrescine transcarbamylase and agmatine deiminase and a snapshot of agmatine deiminase catalyzing its reaction.
  J Bacteriol, 189, 1254-1265.
PDB codes: 2j2t 2jer
16704984 D.Shi, H.Morizono, J.Cabrera-Luque, X.Yu, L.Roth, M.H.Malamy, N.M.Allewell, and M.Tuchman (2006).
Structure and catalytic mechanism of a novel N-succinyl-L-ornithine transcarbamylase in arginine biosynthesis of Bacteroides fragilis.
  J Biol Chem, 281, 20623-20631.
PDB codes: 2fg6 2fg7
16741992 D.Shi, X.Yu, L.Roth, H.Morizono, M.Tuchman, and N.M.Allewell (2006).
Structures of N-acetylornithine transcarbamoylase from Xanthomonas campestris complexed with substrates and substrate analogs imply mechanisms for substrate binding and catalysis.
  Proteins, 64, 532-542.
PDB codes: 1zq2 1zq6 1zq8 3kzm 3kzn 3kzo
16585758 H.Morizono, J.Cabrera-Luque, D.Shi, R.Gallegos, S.Yamaguchi, X.Yu, N.M.Allewell, M.H.Malamy, and M.Tuchman (2006).
Acetylornithine transcarbamylase: a novel enzyme in arginine biosynthesis.
  J Bacteriol, 188, 2974-2982.  
16786505 S.Yamaguchi, L.L.Brailey, H.Morizono, A.E.Bale, and M.Tuchman (2006).
Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene.
  Hum Mutat, 27, 626-632.  
15731101 D.Shi, H.Morizono, X.Yu, L.Roth, L.Caldovic, N.M.Allewell, M.H.Malamy, and M.Tuchman (2005).
Crystal structure of N-acetylornithine transcarbamylase from Xanthomonas campestris: a novel enzyme in a new arginine biosynthetic pathway found in several eubacteria.
  J Biol Chem, 280, 14366-14369.
PDB codes: 1yh0 1yh1 3kzc 3kzk
  16511126 D.Shi, X.Yu, L.Roth, H.Morizono, Y.Hathout, N.M.Allewell, and M.Tuchman (2005).
Expression, purification, crystallization and preliminary X-ray crystallographic studies of a novel acetylcitrulline deacetylase from Xanthomonas campestris.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 676-679.  
11793468 M.Tuchman, N.Jaleel, H.Morizono, L.Sheehy, and M.G.Lynch (2002).
Mutations and polymorphisms in the human ornithine transcarbamylase gene.
  Hum Mutat, 19, 93.  
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.