geranylgeranyltransferase type 1

{{Short description|Macromolecular complex found in Homo sapiens}}

{{hatnote|Geranylgeranyltransferase may be used to refer to either Geranylgeranyltransferase type 1 or Rab geranylgeranyltransferase}}

{{infobox enzyme

| Name = protein geranylgeranyltransferase type I

| EC_number = 2.5.1.59

| CAS_number = 135371-29-8

| GO_code = 0004662

| image =

| width =

| caption =

}}

{{infobox protein

| Name = GGTase 1 α-subunit (farnesyltransferase, CAAX box)

| caption =

| image =

| width =

| HGNCid = 3782

| Symbol = FNTA

| AltSymbols =

| EntrezGene = 2339

| OMIM = 134635

| RefSeq = NM_002027

| UniProt = P49354

| PDB = 1S64

| ECnumber = 2.5.1.59

| Chromosome = 8

| Arm = p

| Band = 11.21

| LocusSupplementaryData =

}}

{{infobox protein

|Name=GGTase 1 β-subunit
(protein geranylgeranyl- transferase type I, β subunit)

|caption=

|image=

|width=

|HGNCid=8895

|Symbol=PGGT1B

|AltSymbols=

|EntrezGene=5229

|OMIM=602031

|RefSeq=NM_005023

|UniProt=P53609

|PDB=1S64

|ECnumber=2.5.1.59

|Chromosome=5

|Arm=q

|Band=23.1

|LocusSupplementaryData=

}}

Geranylgeranyltransferase type 1 or simply geranylgeranyltransferase is one of the three enzymes in the prenyltransferase group. In specific terms, Geranylgeranyltransferase (GGTase 1) adds a 20-carbon isoprenoid called a geranylgeranyl group to proteins bearing a CaaX motif: a four-amino acid sequence at the carboxyl terminal of a protein. Geranylgeranyltransferase inhibitors are being investigated as anti-cancer agents.{{cite journal |vauthors=Lane KT, Beese LS | title = Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I | journal = J. Lipid Res. | volume = 47 | issue = 4 | pages = 681–99 |date=April 2006 | pmid = 16477080 | doi = 10.1194/jlr.R600002-JLR200 | doi-access = free }}

Function

Prenyltransferases, including geranylgeranyltransferase, posttranslationally modify proteins by adding an isoprenoid lipid called a prenyl group to the carboxyl terminus of the target protein. This process, called prenylation, causes prenylated proteins to become membrane-associated due to the hydrophobic nature of the prenyl group. Most prenylated proteins are involved in cellular signaling, wherein membrane association is critical for function.

Structure

Geranylgeranyltransferase contains two subunits, α and β that are encoded by the FNTA and PGGT1B genes, respectively. Both subunits are composed primarily of alpha helices. Geranylgeranyltransferase coordinates a zinc cation on its β subunit at the lip of the active site. Geranylgeranyltransferase has a hydrophobic binding pocket for geranylgeranyl diphosphate, the lipid donor molecule. All Geranylgeranyltransferase substrates invariably have a cysteine as their fourth-to-last residue. This cysteine, coordinated by the zinc, engages in an SN2 type attack on the geranylgeranyl diphosphate, displacing the diphosphate.{{cite journal |vauthors=Reid TS, Terry KL, Casey PJ, Beese LS | title = Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity | journal = J. Mol. Biol. | volume = 343 | issue = 2 | pages = 417–33 |date=October 2004 | pmid = 15451670 | doi = 10.1016/j.jmb.2004.08.056 }}{{cite journal |vauthors=Long SB, Casey PJ, Beese LS | title = Reaction path of protein farnesyltransferase at atomic resolution | journal = Nature | volume = 419 | issue = 6907 | pages = 645–50 |date=October 2002 | pmid = 12374986 | doi = 10.1038/nature00986 | bibcode = 2002Natur.419..645L | s2cid = 4412580 }}

geranylgeranyltransferase type 1

Function

Structure

See also

References

Further reading