Summary: 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase

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Wikipedia: 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase
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This is the Wikipedia entry entitled "2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase". More...

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2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase Edit Wikipedia article

2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase

Identifiers

Databases

PDB structures

AmiGO / EGO

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PMC	articles
PubMed	articles
NCBI	proteins

IspD

2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD) from Arabidopsis thaliana

Identifiers

Symbol

IspD

Pfam clan

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

In enzymology, a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (EC 2.7.7.60) is an enzyme that catalyzes the chemical reaction:

2-C-methyl-D-erythritol 4-phosphate + CTP

\rightleftharpoons

diphosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol

Thus, the two substrates of this enzyme are CTP and 2-C-methyl-D-erythritol 4-phosphate, whereas its two products are diphosphate and 4-diphosphocytidyl-2-C-methylerythritol.

This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases).

This enzyme participates in isoprenoid biosynthesis and stenvenosim. It catalyzes the third step of the MEP pathway; the formation of CDP-ME (4-diphosphocytidyl-2C-methyl-D-erythritol) from CTP and MEP (2C-methyl-D-erythritol 4-phosphate).^[1] The isoprenoid pathway is a well known target for anti-infective drug development.^[2]^[3]

Nomenclature

The systematic name of this enzyme class is CTP:2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase. This enzyme is also called:

MEP cytidylyltransferase
CDP-ME synthetase

It is normally abbreviated IspD. It is also referenced by the open reading frame YgbP.

Structural studies

The crystal structure of the E. coli 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase 1I52, 1INI & 1INJ, reported by Richard et al. (2001), was the first one for an enzyme involved in the MEP pathway.

As of February 2010, 13 other structures have been solved for this class of enzymes, with PDB accession codes 1H3M, 1VGT, 1VGU, 1VGZ, 1VPA, 1VGW, 1W55, 1W57, 1W77,2PX7, 2VSI, 3F1C and 2VSH.

References

^ Rohdich F, Wungsintaweekul J, Eisenreich W, Richter G, Schuhr CA, Hecht S, Zenk MH, Bacher A (June 2000). "Biosynthesis of terpenoids: 4-diphosphocytidyl-2C-methyl-D-erythritol synthase of Arabidopsis thaliana". Proceedings of the National Academy of Sciences of the United States of America. 97 (12): 6451–6. doi:10.1073/pnas.97.12.6451. PMC 18623. PMID 10841550.
^ Illarionova V, Kaiser J, Ostrozhenkova E, Bacher A, Fischer M, Eisenreich W, Rohdich F (November 2006). "Nonmevalonate terpene biosynthesis enzymes as antiinfective drug targets: substrate synthesis and high-throughput screening methods". J. Org. Chem. 71 (23): 8824–34. doi:10.1021/jo061466o. PMID 17081012.
^ Eoh H, Brown AC, Buetow L, Hunter WN, Parish T, Kaur D, Brennan PJ, Crick DC (December 2007). "Characterization of the Mycobacterium tuberculosis 4-diphosphocytidyl-2-C-methyl-D-erythritol synthase: potential for drug development". J. Bacteriol. 189 (24): 8922–7. doi:10.1128/JB.00925-07. PMC 2168624. PMID 17921290.

2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase Provide feedback

Members of this family are enzymes which catalyse the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from cytidine triphosphate and 2-C-methyl-D-erythritol 4-phosphate (MEP) [1].

Literature references

Rohdich F, Wungsintaweekul J, Fellermeier M, Sagner S, Herz S, Kis K, Eisenreich W, Bacher A, Zenk MH;, Proc Natl Acad Sci U S A. 1999;96:11758-11763.: Cytidine 5'-triphosphate-dependent biosynthesis of isoprenoids: YgbP protein of Escherichia coli catalyzes the formation of 4-diphosphocytidyl-2-C-methylerythritol. PUBMED:10518523 EPMC:10518523

Internal database links

SCOOP:	CofC CTP_transf_3 DUF2064 Glyco_tranf_2_3 Glycos_transf_2 NTP_transf_3 NTP_transferase
Similarity to PfamA using HHSearch:	CTP_transf_3 NTP_transf_3

External database links

PROSITE:	PDOC00997
SCOP:	1inj

This tab holds annotation information from the InterPro database.

InterPro entry IPR034683

This family consists of cytidylyltransferases IspD and TarI.

2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD) catalyses the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from CTP and 2-C-methyl-D-erythritol 4-phosphate (MEP) in the deoxyxylulose pathway of isopentenyl diphosphate (IPP) biosynthesis [PUBMED:10841550]. This mevalonate independent pathway that utilizes pyruvate and glyceraldehydes 3-phosphate as starting materials for production of IPP occurs in a variety of bacteria, archaea and plant cells, but is absent in mammals. The isoprenoid pathway is a well known target for anti-infective drug development [PUBMED:17081012, PUBMED:17921290]. In about twenty percent of bacterial genomes, this protein occurs as IspDF, a bifunctional fusion protein.

Ribitol-5-phosphate cytidylyltransferase (TarI) is required for the synthesis of activated ribitol via the wall teichoic acid biosynthesis pathway. The enzyme catalyzes the transfer of the cytidylyl group of CTP to D-ribitol 5-phosphate to form CDP-ribitol [PUBMED:19074383]. The human IspD (known as D-ribitol-5-phosphate cytidylyltransferase or isoprenoid synthase domain-containing protein) shows a canonical N-terminal cytidyltransferase domain linked to a C-terminal domain that is absent in cytidyltransferase homologues. It has cytidyltransferase activity toward pentose phosphates, including ribulose 5-phosphate, ribose 5-phosphate, and ribitol 5-phosphate. It has benn implicated in dystroglycan O-mannosylation [PUBMED:26687144, PUBMED:27194101].

Gene Ontology

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

Molecular function

cytidylyltransferase activity (GO:0070567)

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 GT-A (CL0110), which has the following description:

This is the GT-A clan that contains diverse glycosyltransferases that possess a Rossmann like fold [1].

The clan contains the following 52 members:

Anp1 Branch Caps_synth Cellulose_synt CgtA CHGN Chitin_synth_1 Chitin_synth_2 CofC CTP_transf_3 DUF2064 DUF273 DUF604 Fringe Galactosyl_T GlcNAc Gly_transf_sug Glyco_tranf_2_2 Glyco_tranf_2_3 Glyco_tranf_2_4 Glyco_tranf_2_5 Glyco_trans_2_3 Glyco_transf_15 Glyco_transf_21 Glyco_transf_24 Glyco_transf_25 Glyco_transf_34 Glyco_transf_43 Glyco_transf_49 Glyco_transf_6 Glyco_transf_64 Glyco_transf_7C Glyco_transf_7N Glyco_transf_8 Glyco_transf_88 Glyco_transf_92 Glycos_transf_2 GNT-I IspD Mannosyl_trans3 MGAT2 NTP_transf_3 NTP_transferase Nucleotid_trans Osmo_MPGsynth Pox_P35 RGP Rhamno_transf STELLO TcdA_TcdB UDP-g_GGTase UDPGP

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

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You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (6)	Full (7414)	Representative proteomes				UniProt (21514)	NCBI (68443)	Meta (4670)
	Seed (6)	Full (7414)	RP15 (1832)	RP35 (4853)	RP55 (7267)	RP75 (10336)	UniProt (21514)	NCBI (68443)	Meta (4670)
Jalview	View	View	View	View	View	View	View	View	View
HTML	View
PP/heatmap	₁

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (6)	Full (7414)	Representative proteomes				UniProt (21514)	NCBI (68443)	Meta (4670)
	Seed (6)	Full (7414)	RP15 (1832)	RP35 (4853)	RP55 (7267)	RP75 (10336)	UniProt (21514)	NCBI (68443)	Meta (4670)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (6)	Full (7414)	Representative proteomes				UniProt (21514)	NCBI (68443)	Meta (4670)
	Seed (6)	Full (7414)	RP15 (1832)	RP35 (4853)	RP55 (7267)	RP75 (10336)	UniProt (21514)	NCBI (68443)	Meta (4670)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download	Download	Download

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

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. 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 alignment.

Note: You can also download the data file for the tree.

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:

Prosite

Previous IDs:

UPF0007;

Type:

Family

Sequence Ontology:

SO:0100021

Author:

Finn RD

, Bateman A

, Eberhardt R

Number in seed:

6

Number in full:

7414

Average length of the domain:

217.70 aa

Average identity of full alignment:

31 %

Average coverage of the sequence by the domain:

78.23 %

HMM information

HMM build commands:

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

search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	20.3	20.3
Trusted cut-off	20.3	20.3
Noise cut-off	20.2	20.2

Model length:

221

Family (HMM) version:

19

Download:

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Species distribution

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Archea	Eukaryota
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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. More...

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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, its 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:

superkingdom
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class
order
family
genus
species

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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.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

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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

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

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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 2 interactions for this family. More...

IspD YgbB

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 IspD domain has been found. There are 72 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 sequence.

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v t e Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

v t e Metabolism - non-mevalonate pathway enzymes

DXP synthase DXP reductoisomerase 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase 4-hydroxy-3-methylbut-2-enyl diphosphate reductase

Family: IspD (PF01128)

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Summary: 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase

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2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase Edit Wikipedia article

Contents

Nomenclature

Structural studies

References

Further reading

2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase Provide feedback

Literature references

Internal database links

External database links

InterPro entry IPR034683

Gene Ontology

Domain organisation

Pfam Clan

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

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

Selections

Currently selected:

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

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