6J2L

Crystal structure of Bi-functional enzyme

Summary for 6J2L

• Entry DOI: 10.2210/pdb6j2l/pdb
• Descriptor: Histidine biosynthesis bifunctional protein HisIE, ZINC ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: bi-functional enzyme, hydrolase
• Biological source: Shigella flexneri
• Total number of polymer chains: 2
• Total formula weight: 45904.85

Authors

Zhang, H.,Shang, G.,Wang, Y. (deposition date: 2019-01-01, release date: 2020-01-01, Last modification date: 2024-03-27)

Primary citation

Wang, Y.,Zhang, F.,Nie, Y.,Shang, G.,Zhang, H.
Structural analysis of Shigella flexneri bi-functional enzyme HisIE in histidine biosynthesis.
Biochem.Biophys.Res.Commun., 516:540-545, 2019

PubMed Abstract: Histidine biosynthesis, which is absent in animals, was shown to be highly conserved among gram-negative bacteria, thus making it an attractive target for antibiotic design. There are many fusion forms of enzymes in the histidine biosynthetic pathway and people still have limited knowledge about their domain organizations and catalytic mechanisms, due to the lack of structural information. Here we report the first crystal structure of Shigella flexneri bi-functional enzyme HisIE (SfHisIE) that functions in the 2nd and 3rd steps in the histidine biosynthetic pathway. This structure shows that HisIE exists as dimers with two loops (fusion loop) connecting the individual dimer of HisE and HisI in its N-terminus and C-terminus respectively. Our mutagenesis study shows mutations in this fusion loop are lethal for bacteria indicating the advantage of gene fusion in Histidine biosynthesis. Structural analysis revealed several highly conserved residues in the putative ligand binding grooves of HisE and HisI, showing an evolutionarily conserved catalytic mechanism shared among gram negative-bacteria.

PubMed: 31235255
DOI: 10.1016/j.bbrc.2019.06.099

Experimental method

X-RAY DIFFRACTION (2.17 Å)