“Polyphosphate kinase”的意思、由来-开放百科全书

In enzymology, a polyphosphate kinase ({{EC number|2.7.4.1}}), or polyphosphate polymerase, is an enzyme that catalyzes the formation of polyphosphate from ATP, with chain lengths of up to a thousand or more orthophosphate moieties.^[1]

Thus, the two substrates of this enzyme are ATP and polyphosphate [(phosphate)n], whereas its two products are ADP and polyphosphate extended by one phosphate moiety [(phosphate)n+1].

This enzyme is a membrane protein and goes through an intermediate stage during the reaction where it is autophosphorylated with a phosphate group covalently linked to a basic amino acyl residue through an N-P bond.

Several enzymes catalyze polyphosphate polymerization. Some of these enzymes couple phosphotransfer to transmembrane transport. These enzyme/transporters are categorized in the Transporter Classification Database (TCDB) under the Polyphosphate Polymerase/YidH Superfamily (TC# 4.E.1) and are transferases that transfer phosphoyl groups (phosphotransferases) with polyphosphate as the acceptor. The systematic name of this enzyme class is ATP:polyphosphate phosphotransferase. This enzyme is also called polyphosphoric acid kinase.

Families

The Polyphosphate Polymerase Superfamily (TC# 4.E.1) includes the following families:

The Vacuolar (Acidocalcisome) Polyphosphate Polymerase (V-PPP) Family

Function

CYTH-like superfamily enzymes, which include polyphosphate polymerases, hydrolyze triphosphate-containing substrates and require metal cations as cofactors. They have a unique active site located at the center of an eight-stranded antiparallel beta barrel tunnel (the triphosphate tunnel). The name CYTH originated from the gene designation for bacterial class IV adenylyl cyclases (CyaB), and from thiamine triphosphatase (THTPA). Class IV adenylate cyclases catalyze the conversion of ATP to 3',5'-cyclic AMP (cAMP) and PPi. Thiamine triphosphatase is a soluble cytosolic enzyme which converts thiamine triphosphate to thiamine diphosphate. This domain superfamily also contains RNA triphosphatases, membrane-associated polyphosphate polymerases, tripolyphosphatases, nucleoside triphosphatases, nucleoside tetraphosphatases and other proteins with unknown functions.

The generalized reaction catalyzed by the vectorial polyphosphate polymerases is:^[5]

Structure

VTC2 has three recognized domains: an N-terminal SPX domain, a large central CYTH-like domain and a smaller transmembrane VTC1 (DUF202) domain. The SPX domain is found in Syg1, Pho81, XPR1 (SPX), and related proteins. This domain is found at the amino termini of a variety of proteins. In the yeast protein, Syg1, the N-terminus directly binds to the G-protein beta subunit and inhibits transduction of the mating pheromone signal. Similarly, the N-terminus of the human XPR1 protein binds directly to the beta subunit of the G-protein heterotrimer, leading to increased production of cAMP. Thus, this domain is involved in G-protein associated signal transduction. The N-termini of several proteins involved in the regulation of phosphate transport, including the putative phosphate level sensors, Pho81 from Saccharomyces cerevisiae and NUC-2 from Neurospora crassa, have this domain.

The SPX domains of the S. cerevisiae low-affinity phosphate transporters, Pho87 and Pho90, auto-regulate uptake and prevent efflux. This SPX-dependent inhibition is mediated by a physical interaction with Spl2. NUC-2 contains several ankyrin repeats. Several members of this family are annotated as XPR1 proteins: the xenotropic and polytropic retrovirus receptor confers susceptibility to infection with xenotropic and polytropic murine leukaemia viruses (MLV). Infection by these retroviruses can inhibit XPR1-mediated cAMP signaling and result in cell toxicity and death. The similarity between Syg1 phosphate regulators and XPR1 sequences has been noted, as has the additional similarity to several predicted proteins of unknown function, from Drosophila melanogaster, Arabidopsis thaliana, Caenorhabditis elegans, Schizosaccharomyces pombe, S. cerevisiae, and many other diverse organisms.^[5]

As of 2015, several structures have been solved for this class of enzymes, with PDB accession codes {{PDB link|1XDO}}, {{PDB link|1XDP}}, {{PDB link|2O8R}}, {{PDB link|3CZP}}, {{PDB link|3CZQ}}, {{PDB link|3RHF}}.

The Uncharacterized DUF202/YidH (YidH) Family

Members of the YidH Family are found in bacteria, archaea and eukaryotes. Members of this family include YidH of E. coli (TC# 9.B.51.1.1) which has 115 amino acyl residues and 3 TMSs of α-helical nature.^[6] The first TMS has a low level of hydrophobicity, the second has a moderate level of hydrophobicity, and the third has very hydrophobic character. These traits appear to be characteristic of all members of this family. A representative list of proteins belonging to this family can be found in the Transporter Classification Database. In fungi, a long homologue of 351 aas has a similar 3 TMS DUF202 domain at its extreme C-terminus.

References

1. ^{{cite journal | vauthors = Brown MR, Kornberg A | title = The long and short of it - polyphosphate, PPK and bacterial survival | journal = Trends Biochem. Sci. | volume = 33 | issue = 6 | pages = 284–90 |date=June 2008 | pmid = 18487048 | doi = 10.1016/j.tibs.2008.04.005 | url = }}
2. ^{{cite journal |last1=Docampo |first1=Roberto |last2=Moreno |first2=Silvia N. J. |title=Acidocalcisomes |journal=Cell Calcium |volume=50 |issue=2 |pages=111–119 |date=August 2011 |pmid=21752464 |doi=10.1016/j.ceca.2011.05.012 |pmc=3156361}}
3. ^{{cite book |last1=Docampo |first1=Roberto |displayauthors=etal |title=New insights into the roles of acidocalcisomes and the Contractile Vacuole Complex in osmoregulation in Protists |journal=International Review of Cell and Molecular Biology |volume=305 |issue= |pages=69–113 |date=2013 |pmid=23890380 |doi=10.1016/B978-0-12-407695-2.00002-0 |pmc=3818246|isbn=9780124076952 }}
4. ^¹{{cite journal |last1=Gerasimaitė |first1=R. |last2=Sharma |first2=S. |last3=Desfougères |first3=Y. |last4=Schmidt |first4=A. |last5=Mayer |first5=A. |title=Coupled synthesis and translocation restrains polyphosphate to acidocalcisome-like vacuoles and prevents its toxicity. |journal=J Cell Sci |volume=127 |issue=23 |pages=5093–104 |date=October 2014 |doi=10.1242/jcs.159772 |pmid=25315834}}
5. ^¹²{{cite web|last1=Saier|first1=Milton|title=Transporter Classification Database: 4.E.1. The Vacuolar (Acidocalcisome) Polyphosphate Polymerase (V-PPP) Family|url=http://www.tcdb.org/search/result.php?tc=4.E.1|website=tcdb.org|accessdate=26 December 2015}}
6. ^{{Cite journal| last = Eichmann| first = Cédric| last2 = Orts| first2 = Julien| last3 = Tzitzilonis| first3 = Christos| last4 = Vögeli| first4 = Beat| last5 = Smrt| first5 = Sean| last6 = Lorieau| first6 = Justin| last7 = Riek| first7 = Roland| date = 2014-12-11| title = Intermolecular detergent-membrane protein noes for the characterization of the dynamics of membrane protein-detergent complexes| journal = The Journal of Physical Chemistry B| volume = 118| issue = 49| pages = 14288–14301| doi = 10.1021/jp509137q| issn = 1520-5207| pmid = 25419869}}

Families

The Vacuolar (Acidocalcisome) Polyphosphate Polymerase (V-PPP) Family

Function

Structure

The Uncharacterized DUF202/YidH (YidH) Family

References

Further reading