PDBsum entry 1iji

Transferase

PDB id: 1iji

Contents

Protein chain

354 a.a. *

Ligands

PLP

Waters ×130

* Residue conservation analysis

PDB id:

1iji

Name:

Transferase

Title:

Crystal structure of l-histidinol phosphate aminotransferase with plp

Structure:

Histidinol phosphate aminotransferase. Chain: a. Synonym: l-histidinol-phosphate aminotransferase, imidazole acetol- phosphate transaminase. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.20Å R-factor: 0.213 R-free: 0.257

Authors:

J.Sivaraman,Y.Li,R.Larocque,J.D.Schrag,M.Cygler,A.Matte

Key ref:

J.Sivaraman et al. (2001). Crystal structure of histidinol phosphate aminotransferase (HisC) from Escherichia coli, and its covalent complex with pyridoxal-5'-phosphate and l-histidinol phosphate. J Mol Biol, 311, 761-776. PubMed id: 11518529 DOI: 10.1006/jmbi.2001.4882

Date:

26-Apr-01 Release date: 29-Aug-01

Protein chain

P06986  (HIS8_ECOLI) -  Histidinol-phosphate aminotransferase from Escherichia coli (strain K12)

Seq: 356 a.a.

Struc: 354 a.a.

Enzyme reactions

• Enzyme class: E.C.2.6.1.9 - histidinol-phosphate transaminase.
• Pathway: Histidine Biosynthesis (late stages)
• Reaction: L-histidinol phosphate + 2-oxoglutarate = 3-(imidazol-4-yl)-2-oxopropyl phosphate + 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

DOI no: 10.1006/jmbi.2001.4882

J Mol Biol 311:761-776 (2001)

PubMed id: 11518529

Crystal structure of histidinol phosphate aminotransferase (HisC) from Escherichia coli, and its covalent complex with pyridoxal-5'-phosphate and l-histidinol phosphate.

J.Sivaraman, Y.Li, R.Larocque, J.D.Schrag, M.Cygler, A.Matte.

ABSTRACT

The biosynthesis of histidine is a central metabolic process in organisms ranging from bacteria to yeast and plants. The seventh step in the synthesis of histidine within eubacteria is carried out by a pyridoxal-5'-phosphate (PLP)-dependent l-histidinol phosphate aminotransferase (HisC, EC 2.6.1.9). Here, we report the crystal structure of l-histidinol phosphate aminotransferase from Escherichia coli, as a complex with pyridoxamine-5'-phosphate (PMP) at 1.5 A resolution, as the internal aldimine with PLP, and in a covalent, tetrahedral complex consisting of PLP and l-histidinol phosphate attached to Lys214, both at 2.2 A resolution. This covalent complex resembles, in structural terms, the gem-diamine intermediate that is formed transiently during conversion of the internal to external aldimine.HisC is a dimeric enzyme with a mass of approximately 80 kDa. Like most PLP-dependent enzymes, each HisC monomer consists of two domains, a larger PLP-binding domain having an alpha/beta/alpha topology, and a smaller domain. An N-terminal arm contributes to the dimerization of the two monomers. The PLP-binding domain of HisC shows weak sequence similarity, but significant structural similarity with the PLP-binding domains of a number of PLP-dependent enzymes. Residues that interact with the PLP cofactor, including Tyr55, Asn157, Asp184, Tyr187, Ser213, Lys214 and Arg222, are conserved in the family of aspartate, tyrosine and histidinol phosphate aminotransferases. The imidazole ring of l-histidinol phosphate is bound, in part, through a hydrogen bond with Tyr110, a residue that is substituted by Phe in the broad substrate specific HisC enzymes from Zymomonas mobilis and Bacillus subtilis.Comparison of the structures of the HisC internal aldimine, the PMP complex and the HisC l-histidinol phosphate complex reveal minimal changes in protein or ligand structure. Proton transfer, required for conversion of the gem-diamine to the external aldimine, does not appear to be limited by the distance between substrate and lysine amino groups. We propose that the tetrahedral complex has resulted from non-productive binding of l-histidinol phosphate soaked into the HisC crystals, resulting in its inability to be converted to the external aldimine at the HisC active site.

Selected figure(s)

Figure 7.
Figure 7. Schematic views of HisC-ligand interactions for (a) the complex of HisC with PMP (b) the HisC internal aldimine with PLP (Llp) and (c) the covalent complex of HisC with PLP and Image -histidinol phosphate (Lph). Hydrogen bonds between HisC and the ligands (less than or equal to 3.2 Å) are indicated by broken lines. These Figures were prepared using the program LIGPLOT.[56]

Figure 9.
Figure 9. Schematic diagram showing the structures from the transimination portion of the aminotransferase reaction mechanism. The structures depicted are for (I) internal aldimine, (II) gem-diamine intermediate protonated at substrate N, (III) gem-diamine intermediate protonated at lysine NZ, and (IV) external aldimine.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2001, 311, 761-776) copyright 2001.

Figures were selected by an automated process.