Database accession: MF7000912
Name: Bi-functional enzyme
PDB ID: 6j22
Experimental method: X-ray (2.20 Å)
Assembly: Homodimer
Source organism: Shigella flexneri
Primary publication of the structure:
Wang Y, Zhang F, Nie Y, Shang G, Zhang H
Structural analysis of Shigella flexneri bi-functional enzyme HisIE in histidine biosynthesis.
(2019) Biochem. Biophys. Res. Commun. 516: 540-545
PMID: 31235255
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.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
ATP binding ATP binding
phosphoribosyl-AMP cyclohydrolase activity phosphoribosyl-AMP cyclohydrolase activity
phosphoribosyl-ATP diphosphatase activity phosphoribosyl-ATP diphosphatase activity
Biological process:
amino acid biosynthetic process amino acid biosynthetic process
histidine biosynthetic process L-histidine biosynthetic process
Cellular component:
cytoplasm cytoplasm
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Histidine biosynthesis bifunctional protein HisIE
Source organism: Shigella flexneri
Length: 203 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMLTEQQRRELDWEKTDGLMPVIVQHAVSGEVLMLGYMNPEALDKTIESGKVTFFSRTKQRLWIKGETSGNFLNVVSIAPDCDNDTLLVLANPIGPTCHKGTSSCFGNTAHQWLFLYQLEQLLAERKYADPETSYTAKLYASGTKRIAQKVGEEGVETALAATVHDRFELTNEASDLMYHLLVLLQDQDLDLTTVIENLHKRHQ
UniProtKB AC: P37793 (positions: 2-201)
Coverage: 98%
Name: Histidine biosynthesis bifunctional protein HisIE
Source organism: Shigella flexneri
Length: 203 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMLTEQQRRELDWEKTDGLMPVIVQHAVSGEVLMLGYMNPEALDKTIESGKVTFFSRTKQRLWIKGETSGNFLNVVSIAPDCDNDTLLVLANPIGPTCHKGTSSCFGNTAHQWLFLYQLEQLLAERKYADPETSYTAKLYASGTKRIAQKVGEEGVETALAATVHDRFELTNEASDLMYHLLVLLQDQDLDLTTVIENLHKRHQ
UniProtKB AC: P37793 (positions: 3-201)
Coverage: 98%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Histidine biosynthesis bifunctional protein
Evidence level: Indirect evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
HisIE and MtHISN2 are proteins with with discrete and directly interacting pyrophosphohydrolase and cyclohydrolase domains. They form a tight dimer with large buried interface. The dimer is formed by two mutually swapped polypeptide chains, forming a bilobial protein. The existence of a monomeric form of either PRA-PH or PRA-CH domain is highly improbable. The dimeric form is consistent with the size-exclusion elution profile. In case of HisIE dimerization is very important for catalytic activity, since its catalytic pocket is formed by both protomers. Arg201 from one monomer is required to stabilize helix 4 in the other monomer, thus making it suitable for substrate binding (PMID:31235255, PMID:33958623).
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
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