Database accession: MF7000914
Name: MtHISN2, a bifunctional enzyme
PDB ID: 7bgm
Experimental method: X-ray (1.60 Å)
Assembly: Homodimer
Source organism: Medicago truncatula
Primary publication of the structure:
Witek W, Sliwiak J, Ruszkowski M
Structural and mechanistic insights into the bifunctional HISN2 enzyme catalyzing the second and third steps of histidine biosynthesis in plants.
(2021) Sci Rep 11: 9647
PMID: 33958623
Abstract:
The second and third steps of the histidine biosynthetic pathway (HBP) in plants are catalyzed by a bifunctional enzyme-HISN2. The enzyme consists of two distinct domains, active respectively as a phosphoribosyl-AMP cyclohydrolase (PRA-CH) and phosphoribosyl-ATP pyrophosphatase (PRA-PH). The domains are analogous to single-domain enzymes encoded by bacterial hisI and hisE genes, respectively. The calculated sequence similarity networks between HISN2 analogs from prokaryotes and eukaryotes suggest that the plant enzymes are closest relatives of those in the class of Deltaproteobacteria. In this work, we obtained crystal structures of HISN2 enzyme from Medicago truncatula (MtHISN2) and described its architecture and interactions with AMP. The AMP molecule bound to the PRA-PH domain shows positioning of the N1-phosphoribosyl relevant to catalysis. AMP bound to the PRA-CH domain mimics a part of the substrate, giving insights into the reaction mechanism. The latter interaction also arises as a possible second-tier regulatory mechanism of the HBP flux, as indicated by inhibition assays and isothermal titration calorimetry.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
ATP binding ATP binding
metal ion binding metal ion 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: not assigned
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 hisIE protein
Source organism: Medicago truncatula
Length: 283 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMALSNVHMLQSARGFQKCNLSFSSHGYPRRGYRTNHLAFASMHTSDPKVDSLLDSVKWDNKGLAVAIAQNVDTGAILMQGFANREAVATTISSRKATFYSRSRSSLWTKGETSNNFINVHDVFLDCDRDSIIYLGKPDGPTCHTGAETCYYTPVFDLLKEEEVEGNKLALTSLYALESTISQRKAEVVEENGKPSWTKRLLLNDKLLCSKIREEANELCETLENNEDKSRTASEMADVLYHAMVLLALKDVKVEEVLQVLRQRFSKSGIEEKRSRPTQKSVEN
UniProtKB AC: A0A072U2X9 (positions: 49-264)
Coverage: 76%
Name: Histidine biosynthesis hisIE protein
Source organism: Medicago truncatula
Length: 283 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMALSNVHMLQSARGFQKCNLSFSSHGYPRRGYRTNHLAFASMHTSDPKVDSLLDSVKWDNKGLAVAIAQNVDTGAILMQGFANREAVATTISSRKATFYSRSRSSLWTKGETSNNFINVHDVFLDCDRDSIIYLGKPDGPTCHTGAETCYYTPVFDLLKEEEVEGNKLALTSLYALESTISQRKAEVVEENGKPSWTKRLLLNDKLLCSKIREEANELCETLENNEDKSRTASEMADVLYHAMVLLALKDVKVEEVLQVLRQRFSKSGIEEKRSRPTQKSVEN
UniProtKB AC: A0A072U2X9 (positions: 49-265)
Coverage: 76%
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)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
