PDBsum entry 4phc

Ligase

PDB id: 4phc

Contents

Protein chains

444 a.a.

Ligands

HIS ×4

GOL ×4

Waters ×55

PDB id:

4phc

Name:

Ligase

Title:

Crystal structure of a human cytosolic histidyl-tRNA synthetase, histidine-bound

Structure:

Histidine--tRNA ligase, cytoplasmic. Chain: a, b, c, d. Synonym: histidyl-tRNA synthetase,hisrs. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hars, hrs. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.84Å R-factor: 0.202 R-free: 0.238

Authors:

C.Y.Koh,A.B.Wetzel,W.J.De Van Der Schueren,W.G.J.Hol

Key ref:

C.Y.Koh et al. (2014). Comparison of histidine recognition in human and trypanosomatid histidyl-tRNA synthetases. Biochimie, 106, 111-120. PubMed id: 25151410 DOI: 10.1016/j.biochi.2014.08.005

Date:

06-May-14 Release date: 27-Aug-14

Protein chains

P12081  (SYHC_HUMAN) -  Histidine--tRNA ligase, cytoplasmic from Homo sapiens

Seq: 509 a.a.

Struc: 444 a.a.

Enzyme reactions

• Enzyme class: E.C.6.1.1.21 - histidine--tRNA ligase.
• Reaction: tRNA(His) + L-histidine + ATP = L-histidyl-tRNA(His) + AMP + diphosphate + H⁺

tRNA(His) + L-histidine (Bound ligand (Het Group name = HIS) corresponds exactly) + ATP = L-histidyl-tRNA(His) + AMP + diphosphate + H(+)

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

reference

DOI no: 10.1016/j.biochi.2014.08.005

Biochimie 106:111-120 (2014)

PubMed id: 25151410

Comparison of histidine recognition in human and trypanosomatid histidyl-tRNA synthetases.

C.Y.Koh, A.B.Wetzel, W.J.de van der Schueren, W.G.Hol.

ABSTRACT

As part of a project aimed at obtaining selective inhibitors and drug-like compounds targeting tRNA synthetases from trypanosomatids, we have elucidated the crystal structure of human cytosolic histidyl-tRNA synthetase (Hs-cHisRS) in complex with histidine in order to be able to compare human and parasite enzymes. The resultant structure of Hs-cHisRS•His represents the substrate-bound state (H-state) of the enzyme. It provides an interesting opportunity to compare with ligand-free and imidazole-bound structures Hs-cHisRS published recently, both of which represent the ligand-free state (F-state) of the enzyme. The H-state Hs-cHisRS undergoes conformational changes in active site residues and several conserved motif of HisRS, compared to F-state structures. The histidine forms eight hydrogen bonds with HisRS of which six engage the amino and carboxylate groups of this amino acid. The availability of published imidazole-bound structure provides a unique opportunity to dissect the structural roles of individual chemical groups of histidine. The analysis revealed the importance of the amino and carboxylate groups, of the histidine in leading to these dramatic conformational changes of the H-state. Further, comparison with previously published trypanosomatid HisRS structures reveals a pocket in the F-state of the parasite enzyme that may provide opportunities for developing specific inhibitors of Trypanosoma brucei HisRS.