Summary: ATP phosphoribosyltransferase

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Wikipedia: ATP phosphoribosyltransferase
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ATP phosphoribosyltransferase

Identifiers

Databases

PDB structures

AmiGO / EGO

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PMC	articles
PubMed	articles

ATP phosphoribosyltransferase

structure of the e.coli atp-phosphoribosyltransferase

Identifiers

Symbol

HisG

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

HisG, C-terminal domain

atp phosphoribosyltransferase (atp-prtase) from mycobacterium tuberculosis in complex with amp and histidine

Identifiers

Symbol

HisG_C

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

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 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.

[edit] Structural studies

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.

[edit] References

^ 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.
^ 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. PMC 17719. PMID 10430882. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=17719.
^ 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.
^ 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.

[edit] Further Reading

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.

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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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ATP phosphoribosyltransferase

No Pfam abstract.

Clan

This family is a member of clan PBP (CL0177), which has a total of 23 members.

External database links

PANDIT:	PF01634
PROSITE:	PDOC01020
Pseudofam:	PF01634
SCOP:	1nh8
SYSTERS:	HisG

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

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Cellular component	cytoplasm (GO:0005737)
Molecular function	ATP phosphoribosyltransferase activity (GO:0003879)
Biological process	histidine biosynthetic process (GO:0000105)

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan PBP (CL0177), which 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

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

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Alignment:	Seed (18) Full (2498) NCBI (1895) Metagenomics (1996)
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Alignment:	Seed (18) Full (2498)
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Sequence:	Inserts lower case All upper case
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Very large alignments can often cause problems for the formatting tool above. If you find that downloading or viewing a large alignment is problematic, you can also download a gzip-compressed, Stockholm-format file containing the seed or full alignment for this family.

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

Pfam alignments:	Seed (18) Full (2498) NCBI (1895) Metagenomics (1996)
Full length sequences	Full-sequences (2498)

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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Trees

This page displays the phylogenetic tree for this family. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed or full alignments.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Pfam-B_1142 (release 4.1)

Previous IDs:

none

Type:

Family

Author:

Bateman A

Number in seed:

18

Number in full:

2498

Average length of the domain:

161.90 aa

Average identity of full alignment:

36 %

Average coverage of the sequence by the domain:

61.27 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 15929002 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	25.5	25.5
Trusted cut-off	26.1	25.5
Noise cut-off	25.1	25.4

Model length:

163

Family (HMM) version:

13

Download:

download the raw HMM for this family

Species distribution

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Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab if you need to select sub-trees and view sequence alignments. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, it's distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

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Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

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Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

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Species trees

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Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

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Interactions

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

tRNA-synt_2b HisG 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 22 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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Family: HisG (PF01634)

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Summary: ATP phosphoribosyltransferase

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ATP phosphoribosyltransferase

[edit] Structural studies

[edit] References

[edit] Further Reading

ATP phosphoribosyltransferase

Clan

External database links

InterPro entry IPR013820

Gene Ontology

Domain organisation

Pfam Clan

Alignments

Viewing

Downloading

View options

Formatting options

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Interactions

Structures