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24  structures 3572  species 3  interactions 3683  sequences 11  architectures

Family: HisG (PF01634)

Summary: ATP phosphoribosyltransferase

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ATP phosphoribosyltransferase Edit Wikipedia article

ATP phosphoribosyltransferase
Identifiers
EC number 2.4.2.17
CAS number 9031-46-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO
ATP phosphoribosyltransferase
PDB 1h3d EBI.jpg
structure of the e.coli atp-phosphoribosyltransferase
Identifiers
Symbol HisG
Pfam PF01634
Pfam clan CL0177
InterPro IPR013820
PROSITE PDOC01020
SCOP 1nh8
SUPERFAMILY 1nh8
HisG, C-terminal domain
PDB 1nh8 EBI.jpg
atp phosphoribosyltransferase (atp-prtase) from mycobacterium tuberculosis in complex with amp and histidine
Identifiers
Symbol HisG_C
Pfam PF08029
Pfam clan CL0089
InterPro IPR013115

In enzymology, an ATP phosphoribosyltransferase (EC 2.4.2.17) is an enzyme that catalyzes the chemical reaction

1-(5-phospho-D-ribosyl)-ATP + diphosphate \rightleftharpoons ATP + 5-phospho-alpha-D-ribose 1-diphosphate

Thus, the two substrates of this enzyme are 1-(5-phospho-D-ribosyl)-ATP and diphosphate, whereas its two products are ATP and 5-phospho-alpha-D-ribose 1-diphosphate.

This enzyme belongs to the family of glycosyltransferases, specifically the pentosyltransferases. The systematic name of this enzyme class is 1-(5-phospho-D-ribosyl)-ATP:diphosphate phospho-alpha-D-ribosyl-transferase. Other names in common use include phosphoribosyl-ATP pyrophosphorylase, adenosine triphosphate phosphoribosyltransferase, phosphoribosyladenosine triphosphate:pyrophosphate, phosphoribosyltransferase, phosphoribosyl ATP synthetase, phosphoribosyl ATP:pyrophosphate phosphoribosyltransferase, phosphoribosyl-ATP:pyrophosphate-phosphoribosyl phosphotransferase, phosphoribosyladenosine triphosphate pyrophosphorylase, and phosphoribosyladenosine triphosphate synthetase.

This enzyme catalyses the first step in the biosynthesis of histidine in bacteria, fungi and plants. It is a member of the larger phosphoribosyltransferase superfamily of enzymes which catalyse the condensation of 5-phospho-alpha-D-ribose 1-diphosphate with nitrogenous bases in the presence of divalent metal ions.[1]

Histidine biosynthesis is an energetically expensive process and ATP phosphoribosyltransferase activity is subject to control at several levels. Transcriptional regulation is based primarily on nutrient conditions and determines the amount of enzyme present in the cell, while feedback inihibition rapidly modulates activity in response to cellular conditions. The enzyme has been shown to be inhibited by 1-(5-phospho-D-ribosyl)-ATP, histidine, ppGpp (a signal associated with adverse environmental conditions) and ADP and AMP (which reflect the overall energy status of the cell). As this pathway of histidine biosynthesis is present only in prokaryotes, plants and fungi, this enzyme is a promising target for the development of novel antimicrobial compounds and herbicides.

ATP phosphoribosyltransferase is found in two distinct forms: a long form containing two catalytic domains and a C-terminal regulatory domain, and a short form in which the regulatory domain is missing. The long form is catalytically competent, but in organisms with the short form, a histidyl-tRNA synthetase paralogue, HisZ, is required for enzyme activity.[2]

The structures of the long form enzymes from Escherichia coli and Mycobacterium tuberculosis have been determined.[3][4] The enzyme itself exists in equilibrium between an active dimeric form, an inactive hexameric form and higher aggregates. Interconversion between the various forms is largely reversible and is influenced by the binding of the natural substrates and inhibitors of the enzyme. The two catalytic domains are linked by a two-stranded beta-sheet and together form a "periplasmic binding protein fold". A crevice between these domains contains the active site. The C-terminal domain is not directly involved in catalysis but appears to be involved the formation of hexamers, induced by the binding of inhibitors such as histidine to the enzyme, thus regulating activity.

Structural studies[edit]

As of late 2007, 10 structures have been solved for this class of enzymes, with PDB accession codes 1H3D, 1NH7, 1NH8, 1O63, 1O64, 1Q1K, 1USY, 1VE4, 1Z7M, and 1Z7N.

References[edit]

  1. ^ Sinha SC, Smith JL (December 2001). "The PRT protein family". Curr. Opin. Struct. Biol. 11 (6): 733–9. doi:10.1016/S0959-440X(01)00274-3. PMID 11751055. 
  2. ^ Sissler M, Delorme C, Bond J, Ehrlich SD, Renault P, Francklyn C (August 1999). "An aminoacyl-tRNA synthetase paralog with a catalytic role in histidine biosynthesis". Proc. Natl. Acad. Sci. U.S.A. 96 (16): 8985–90. doi:10.1073/pnas.96.16.8985. PMC 17719. PMID 10430882. 
  3. ^ Lohkamp B, McDermott G, Campbell SA, Coggins JR, Lapthorn AJ (February 2004). "The structure of Escherichia coli ATP-phosphoribosyltransferase: identification of substrate binding sites and mode of AMP inhibition". J. Mol. Biol. 336 (1): 131–44. doi:10.1016/j.jmb.2003.12.020. PMID 14741209. 
  4. ^ Cho Y, Sharma V, Sacchettini JC (March 2003). "Crystal structure of ATP phosphoribosyltransferase from Mycobacterium tuberculosis". J. Biol. Chem. 278 (10): 8333–9. doi:10.1074/jbc.M212124200. PMID 12511575. 

Further reading[edit]

  • AMES BN, MARTIN RG, GARRY BJ (1961). "The first step of histidine biosynthesis". J. Biol. Chem. 236: 2019–26. PMID 13682989. 
  • Martin RG (1963). "The phosphorolysis of nucleosides by rabbit bone marrow: The nature of feedback inhibition by histidine". J. Biol. Chem. 238: 257–268. 
  • Voll MJ, Appella E, Martin RG (1967). "Purification and composition studies of phosphoribosyladenosine triphosphate:pyrophosphate phosphoribosyltransferase, the first enzyme of histidine biosynthesis". J. Biol. Chem. 242 (8): 1760–7. PMID 5337591. 

This article incorporates text from the public domain Pfam and InterPro IPR013820

This article incorporates text from the public domain Pfam and InterPro IPR013115

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This tab holds annotation information from the InterPro database.

InterPro entry IPR013820

ATP phosphoribosyltransferase (EC) is the enzyme that catalyzes the first step in the biosynthesis of histidine in bacteria, fungi and plants as shown below. It is a member of the larger phosphoribosyltransferase superfamily of enzymes which catalyse the condensation of 5-phospho-alpha-D-ribose 1-diphosphate with nitrogenous bases in the presence of divalent metal ions [PUBMED:11751055]. ATP + 5-phospho-alpha-D-ribose 1-diphosphate = 1-(5-phospho-D-ribosyl)-ATP + diphosphate Histidine biosynthesis is an energetically expensive process and ATP phosphoribosyltransferase activity is subject to control at several levels. Transcriptional regulation is based primarily on nutrient conditions and determines the amount of enzyme present in the cell, while feedback inihibition rapidly modulates activity in response to cellular conditions. The enzyme has been shown to be inhibited by 1-(5-phospho-D-ribosyl)-ATP, histidine, ppGpp (a signal associated with adverse environmental conditions) and ADP and AMP (which reflect the overall energy status of the cell). As this pathway of histidine biosynthesis is present only in prokayrotes, plants and fungi, this enzyme is a promising target for the development of novel antimicrobial compounds and herbicides.

ATP phosphoribosyltransferase is found in two distinct forms: a long form containing two catalytic domains and a C-terminal regulatory domain, and a short form in which the regulatory domain is missing. The long form is catalytically competent, but in organisms with the short form, a histidyl-tRNA synthetase paralogue, HisZ, is required for enzyme activity [PUBMED:10430882]. This entry represents the catalytic region of this enzyme.

The structures of the long form enzymes from Escherichia coli (SWISSPROT) and Mycobacterium tuberculosis (SWISSPROT) have been determined [PUBMED:14741209, PUBMED:12511575]. The enzyme itself exists in equilibrium between an active dimeric form, an inactive hexameric form and higher aggregates. Interconversion between the various forms is largely reversible and is influenced by the binding of the natural substrates and inhibitors of the enzyme. The two catalytic domains are linked by a two-stranded beta-sheet and togther form a "periplasmic binding protein fold". A crevice between these domains contains the active site. The C-terminal domain is not directly involved in catalysis but appears to be involved the formation of hexamers, induced by the binding of inhibitors such as histidine to the enzyme, thus regulating activity.

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan PBP (CL0177), which has the following description:

Periplasmic binding proteins (PBPs) consist of two large lobes that close around the bound ligand. This architecture is reiterated in transcriptional regulators, such as the lac repressors. In the process of evolution, genes encoding the PBPs have fused with genes for integral membrane proteins. Thus, diverse mammalian receptors contain extracellular ligand binding domains that are homologous to the PBPs; these include glutamate/glycine-gated ion channels such as the NMDA receptor, G protein-coupled receptors, including metabotropic glutamate, GABA-B, calcium sensing, and pheromone receptors, and atrial natriuretic peptide-guanylate cyclase receptors [2].

The clan contains the following 23 members:

DUF3834 HisG Lig_chan-Glu_bd Lipoprotein_8 Lipoprotein_9 LysR_substrate Mycoplasma_p37 NMT1 NMT1_2 OpuAC PBP_like PBP_like_2 Phosphonate-bd SBP_bac_1 SBP_bac_11 SBP_bac_3 SBP_bac_5 SBP_bac_6 SBP_bac_7 SBP_bac_8 TctC Transferrin VitK2_biosynth

Alignments

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(18)
Full
(3683)
Representative proteomes NCBI
(2521)
Meta
(1995)
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(333)
RP35
(672)
RP55
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RP75
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  Seed
(18)
Full
(3683)
Representative proteomes NCBI
(2521)
Meta
(1995)
RP15
(333)
RP35
(672)
RP55
(875)
RP75
(1021)
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  Seed
(18)
Full
(3683)
Representative proteomes NCBI
(2521)
Meta
(1995)
RP15
(333)
RP35
(672)
RP55
(875)
RP75
(1021)
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Curation and family details

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Seed source: Pfam-B_1142 (release 4.1)
Previous IDs: none
Type: Family
Author: Bateman A
Number in seed: 18
Number in full: 3683
Average length of the domain: 161.50 aa
Average identity of full alignment: 36 %
Average coverage of the sequence by the domain: 61.55 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.5 25.5
Trusted cut-off 26.0 25.5
Noise cut-off 25.1 25.4
Model length: 163
Family (HMM) version: 13
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Species distribution

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Interactions

There are 3 interactions for this family. More...

HisG tRNA-synt_2b HisG_C

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the HisG domain has been found. There are 24 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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