PDBsum entry 1c9y

Transferase

PDB id: 1c9y

Contents

Protein chain

321 a.a. *

Ligands

NVA

_CP

Waters ×223

* Residue conservation analysis

PDB id:

1c9y

Name:

Transferase

Title:

Human ornithine transcarbamylase: crystallographic insights into substrate recognition and catalytic mechanism

Structure:

Ornithine carbamoyltransferase. Chain: a. Synonym: otcase, ornithine transcarbamylase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Trimer (from PDB file)

Resolution:

1.90Å R-factor: 0.187 R-free: 0.208

Authors:

D.Shi,X.Yu,H.Morizono,M.Tuchman,N.M.Allewell

Key ref:

D.Shi et al. (2000). Crystal structure of human ornithine transcarbamylase complexed with carbamoyl phosphate and L-norvaline at 1.9 A resolution. Proteins, 39, 271-277. PubMed id: 10813810 DOI: 10.1002/(SICI)1097-0134(20000601)39:4<271::AID-PROT10>3.3.CO;2-5

Date:

03-Aug-99 Release date: 06-Jun-00

Protein chain

P00480  (OTC_HUMAN) -  Ornithine transcarbamylase, mitochondrial from Homo sapiens

Seq: 354 a.a.

Struc: 322 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.2.1.3.3 - ornithine carbamoyltransferase.
• Pathway: Urea Cycle and Arginine Biosynthesis
• Reaction: carbamoyl phosphate + L-ornithine = L-citrulline + phosphate + H⁺

carbamoyl phosphate (Bound ligand (Het Group name = CP) corresponds exactly) + L-ornithine (Bound ligand (Het Group name = NVA) matches with 88.89% similarity) = L-citrulline + phosphate + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1002/(SICI)1097-0134(20000601)39:4<271::AID-PROT10>3.3.CO;2-5

Proteins 39:271-277 (2000)

PubMed id: 10813810

Crystal structure of human ornithine transcarbamylase complexed with carbamoyl phosphate and L-norvaline at 1.9 A resolution.

D.Shi, H.Morizono, M.Aoyagi, M.Tuchman, N.M.Allewell.

ABSTRACT

The crystal structure of human ornithine transcarbamylase (OTCase) complexed with carbamoyl phosphate (CP) and L-norvaline (NOR) has been determined to 1.9-A resolution. There are significant differences in the interactions of CP with the protein, compared with the interactions of the CP moiety of the bisubstrate analogue N-(phosphonoacetyl)-L-ornithine (PALO). The carbonyl plane of CP rotates about 60 degrees compared with the equivalent plane in PALO complexed with OTCase. This positions the side chain of NOR optimally to interact with the carbonyl carbon of CP. The mixed-anhydride oxygen of CP, which is analogous to the methylene group in PALO, interacts with the guanidinium group of Arg-92; the primary carbamoyl nitrogen interacts with the main-chain carbonyl oxygens of Cys-303 and Leu-304, the side chain carbonyl oxygen of Gln-171, and the side chain of Arg-330. The residues that interact with NOR are similar to the residues that interact with the ornithine (ORN) moiety of PALO. The side chain of NOR is well defined and close to the side chain of Cys-303 with the side chains of Leu-163, Leu-200, Met-268, and Pro-305 forming a hydrophobic wall. C-delta of NOR is close to the carbonyl oxygen of Leu-304 (3.56 A), S-gamma atom of Cys-303 (4.19 A), and carbonyl carbon of CP (3.28 A). Even though the N-epsilon atom of ornithine is absent in this structure, the side chain of NOR is positioned to enable the N-epsilon of ornithine to donate a hydrogen to the S-gamma atom of Cys-303 along the reaction pathway. Binding of CP and NOR promotes domain closure to the same degree as PALO, and the active site structure of CP-NOR-enzyme complex is similar to that of the PALO-enzyme complex. The structures of the active sites in the complexes of aspartate transcarbamylase (ATCase) with various substrates or inhibitors are similar to this OTCase structure, consistent with their common evolutionary origin.

Selected figure(s)

Figure 1.
Figure 1. Schematic drawing of the reaction catalyzed by OTCase.

Figure 6.
Figure 6. Schematic drawing of the proposed catalytic mechanism.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2000, 39, 271-277) copyright 2000.

Figures were selected by an automated process.