File Prenylgroup.png thumb Prenyl the functional group Prenylation , or isoprenylation , or lipidation is the addition of hydrophobic molecules to a protein . It is usually assumed that prenyl groups 3 methyl 2 buten 1 yl facilitate attachment to cell membrane s, similar to lipid anchored protein lipid anchor like the GPI anchor , though direct evidence is missing. Prenyl groups have been shown to be important for protein protein binding through specialized prenyl binding domains. Protein prenylation Protein prenylation involves the transfer of either a farnesyl or a geranyl geranyl moiety to C terminal cysteine s of the target protein. There are three enzymes that carry out prenylation in the cell, farnesyl transferase, Caax protease and methyl transferase. Farnesyltransferase and geranylgeranyltransferase I Farnesyltransferase and Geranylgeranyltransferase type 1 Geranylgeranyltransferase I are very similar proteins. They consist of two subunits, the subunit which is common to both enzymes, and the subunit whose sequence identity is just 25 . These enzymes recognise the CaaX box at the C terminus of the target protein. C is the cysteine that is prenylated, a is any aliphatic amino ... of protein prenylation motifs and establishment of an on line analysis facility entitled http mendel.imp.univie.ac.at ... out the prenylation reaction with the isoprenoid alcohol. However, enzymatic activity for isoprenoid ... can be involved in prenylation, likely via phosphorylation to the corresponding isoprenoid diphosphate. Proteins that undergo prenylation include Ras protein Ras , which plays a central role in the development of cancer . This suggests that inhibitors of prenylation enzymes e.g. farnesyltransferase ... due to effects on Rab G protein Rab prenylation as on Ras prenylation. Farnesyltransferase ... of protein prenylation motifs . Genome Biology . 6 R55. cite journal author Magee A, Seabra ... emboj cdg571 pmc 275430 External links MeshName Prenylation Protein posttranslational modification ... more details
Unreferenced date March 2007 Geranylgeranylation is a form of prenylation , which is a post translational modification of proteins that involves the attachment of one or two 20 carbon lipophilic geranylgeranyl isoprene units from geranylgeranyl diphosphate to one or two cysteine residue s at the C terminus of specific proteins. Prenylation including geranylgeranylation is thought to function, at least in part, as a membrane anchor for proteins. The process of geranylgeranylation can be catalyzed by either Geranylgeranyltransferase type 1 geranylgeranyl transferase I GGTase I or Rab geranylgeranyltransferase Rab GGTase also GGTase II . GGTase I catalyzes the addition of one geranylgeranyl group onto the C terminal consensus sequence CAAL somewhat similar to farnesyltransferase reactions , where C cysteine, A any aliphatic amino acid, and L leucine. Rab GGTase adds a total of two geranylgeranyl groups onto two cysteine residues at the C terminal consensus sequence CXC or XXCC. The source of the geranylgeranyl group is geranylgeranyl diphosphate, which is synthesized from the isoprenoid biosynthetic pathway. An example of this can be seen in the lipid anchor ing of the Rho GTP binding protein Rho GTPase family of signaling molecule s and the gamma subunit of heterotrimeric G proteins . For more information see prenylation . Category Proteins Category Gene expression Category Molecular biology protein stub ... more details
In lipid anchored proteins , a covalently attached fatty acid such as palmitate or myristate serves to anchor them to either face of the cell membrane . Examples include G protein s and certain kinase s. It is believed that the fatty acid chain inserts and assumes a place in the lipid bilayer bilayer structure of the membrane alongside the similar fatty acid tails of the surrounding lipid molecules. Potential points of attachment include the terminal amino group of the protein backbone and the side chain of cysteine residues. Prenylation is the attachment of lipid chains to proteins to facilitate their interaction with the cell membrane . Some important prenylation chains are geranylgeraniol , farnesol and dolichol , all products of the HMG CoA reductase metabolic pathway . Other anchors include the GPI anchor see there . The bond is covalent. ref name Karp2009 cite book author Gerald Karp title Cell and Molecular Biology Concepts and Experiments url http books.google.com books?id arRGYE0GxRQC&pg PA128 accessdate 13 November 2010 year 2009 publisher John Wiley and Sons isbn 9780470483374 pages 128 ref References Reflist Cell membranes DEFAULTSORT Lipid Anchored Protein Category Membrane biology Category Membrane proteins Category Lipoproteins Category Posttranslational modification Membrane protein stub sr Lipid vezani proteini ... more details
protein Name RAB27A RAB27A, member RAS oncogene family caption image width HGNCid 9766 Symbol RAB27A AltSymbols EntrezGene 5873 OMIM 603868 RefSeq NM 004580 UniProt P51159 PDB ECnumber Chromosome 15 Arm q Band 21 LocusSupplementaryData protein Name RAB27B, member RAS oncogene family caption image width HGNCid 9767 Symbol RAB27B AltSymbols EntrezGene 5874 OMIM 603869 RefSeq NM 004163 UniProt O00194 PDB ECnumber Chromosome 18 Arm q Band 21.2 LocusSupplementaryData Rab27 is a member of the Rab G protein Rab subfamily of GTPase s. Rab27 is post translationally modified by the addition of two prenylation geranylgeranyl groups on the two C terminal cysteine s. Pathology Mutations that prevent the expression of Rab27 knock out mutations cause the hypopigmentation and immunodefficiency disorder known as type II Griscelli syndrome , while a decrease in Rab27 prenylation is thought to be involved in choroideremia . The symptoms of type II Griscelli syndrome have shown that Rab27 is involved in melanosome transport in melanocytes and in cytotoxic killing activity in cytotoxic T lymphoblasts . In melanocytes Rab27 binds the melanosome. The melanosome is transported along the microtubule . Rab27 then recruits Slac2A and myosin Va, these enzymes are essential for the transfer of the melanosomes from the microtubules to actin filaments. The melanosomes can now continue on their path towards the cell periphery. If either Rab27, Slac2A or myosin Va are absent then the melansomes remain in the perinuclear region of the cell. This disruption in pigmentation results in the hypopigmentation seen in the silvery hair colour of patients with Griscelli syndrome . External links MeshName RAB27A protein, human MeshName RAB27B protein, human Category Signal transduction Category EC 3.6.5 biochemistry stub Acid anhydride hydrolases ... more details
Image Tetrapeptide structural formulae v.1.png miniatur thumb 500px A tetrapeptide example Valine Val Glycine Gly Serine Ser Alanine Ala with span style color green green span highlighted N terminal amino acid example L valine and span style color blue blue span marked C terminal amino acid examplel L alanine . The C terminus also known as the carboxyl terminus , carboxy terminus , C terminal tail , C terminal end , or COOH terminus of a protein or polypeptide is the end of the amino acid chain terminated by a free carboxyl group COOH . When the protein is translated from messenger RNA, it is created from N terminus to C terminus. The convention for writing peptide sequences is to put the C terminal end on the right and write the sequence from N to C terminus. Chemistry Each amino acid has a carboxyl group and an amine group, and amino acids link to one another to form a chain by a dehydration reaction by joining the amine group of one amino acid to the carboxyl group of the next. Thus polypeptide chains have an end with an unbound carboxyl group, the C terminus, and an end with an amine group, the N terminal end N terminus . Proteins are naturally synthesized starting from the N terminus and ending at the C terminus. Function C terminal retention signals While the N terminus of a protein often contains targeting signals, the C terminus can contain retention signals for protein sorting. The most common ER retention signal is the amino acid sequence KDEL or HDEL at the C terminus, which keeps the protein in the endoplasmic reticulum and prevents it from entering the secretory pathway . C terminal modifications The C terminus of proteins can be modified posttranslational modification posttranslationally , most commonly by the addition of a lipid anchor to the C terminus that allows the protein to be inserted into a membrane without having a transmembrane domain . Prenylation main Prenylation One form of C terminal modification is prenylation . During prenylation, ... more details
for the largest number of individual protein prenylation events in the cell, ref name pmid18756270 ... of protein prenylation journal EMBO J. volume 27 issue 18 pages 2444 56 year 2008 month ... sup 2 sup and a zinc ion Zn sup 2 sup , all of which interact with the beta subunit. See also Prenylation ... of Rabnext term geranylgeranyl transferase disrupt the prenylation and membrane localization of previous ... more details
Oxysterols are oxidized derivatives of cholesterol , which are important in many biological processes, including cholesterol homeostasis , sphingolipid metabolism, platelet aggregation, apoptosis, and protein prenylation . ref cite journal pmid 10617772 year 2000 month Jan author Schroepfer, Gj, Jr title Oxysterols modulators of cholesterol metabolism and other processes volume 80 issue 1 pages 361 554 issn 0031 9333 journal Physiological reviews url http physrev.physiology.org cgi pmidlookup?view long&pmid 10617772 format Free full text ref References references External links cite journal journal Arteriosclerosis, Thrombosis, and Vascular Biology year 2002 volume 22 issue 5 pages 734 title Oxysterols Friends, Foes, or Just Fellow Passengers? author Ingemar Bj rkhem Ulf Diczfalusy url http atvb.ahajournals.org cgi content abstract 22 5 734 doi 10.1161 01.ATV.0000013312.32196.49 pmid 12006384 cite journal doi 10.1172 JCI16388 url http www.jci.org articles view 16388 year 2002 month Sep author Bj rkhem, I title Do oxysterols control cholesterol homeostasis? volume 110 issue 6 pages 725 30 pmid 12235099 pmc 151135 journal The Journal of clinical investigation Category Sterols chem stub ... more details
Orphan date February 2009 The PT barrel , is a new protein fold. The PT Barrel Fold Image orf2 anim1X.gif right Animated view of a PT barrel PDB accession code 1ZB6,1ZDY,1ZDW,1CZW . It consists of a closed sheet comprising ten anti parallel beta sheet strands arranged around a central barrel core, itself surrounded by a ring of alpha helix helices forming the outer, solvent exposed surface of the barrel. The secondary connectivity nearly conforms to an 5 classification, but is more specifically described using the 4 nomenclature, where helices 6 and 8, both involved in inter protein contacts in the crystal lattice, display a helical kink . The most hydrophobic section of the PT barrel is the region residing between the outer surface of the cylindrical barrel and the belt of surrounding helices. Additionally, a number of hydrophobic residues located inside the barrel accommodate the prenyl tail of the Geranyl diPhosphate GPP and GSPP molecules, while the diphosphate or the thio diphosphate head groups of substrate and substrate analogs, respectively, point toward the upper , more polar end of the barrel where a Mg sup 2 sup ion is coordinated. Finally, the bottom of the barrel is capped by a short C terminal helix 11 . References cite journal author Kuzuyama T, Noel JP, Richard SB title Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products journal Nature volume 435 issue 7044 pages 983 7 year 2005 month June pmid 15959519 pmc 2874460 doi 10.1038 nature0366810.1038 nature03668 cite journal author Koehl P title Relaxed specificity in aromatic prenyltransferases journal Nat. Chem. Biol. volume 1 issue 2 pages 71 2 year 2005 month July pmid 16408001 doi 10.1038 nchembio0705 7110.1038 nchembio0705 71 cite journal author Botta B, Delle Monache G, Menendez P, Boffi A title Novel prenyltransferase enzymes as a tool for flavonoid prenylation journal Trends Pharmacol. Sci. volume 26 issue 12 pages 606 8 year 200 ... more details
enzyme Name Rab protein geranylgeranyltransferase EC number 2.5.1.60 CAS number IUBMB EC number 2 5 1 60 GO code 0004663 image width caption In enzymology , a protein geranylgeranyltransferase type II EC number 2.5.1.60 is an enzyme that catalysis catalyzes the chemical reaction geranylgeranyl diphosphate protein cysteine math rightleftharpoons math S geranylgeranyl protein diphosphate Thus, the two substrate biochemistry substrates of this enzyme are geranylgeranyl diphosphate and protein cysteine , whereas its two product chemistry products are S geranylgeranyl protein and diphosphate . This enzyme belongs to the family of transferase s, specifically those transferring aryl or alkyl groups other than methyl groups. The systematic name of this enzyme class is geranylgeranyl diphosphate protein cysteine geranyltransferase . Other names in common use include GGTaseII , Rab geranylgeranyltransferase , RabGGTase , geranylgeranyl diphosphate,geranylgeranyl diphosphate protein , and cysteine geranyltransferase . References reflist 1 cite journal author Casey PJ, Seabra MC date 1996 title Protein prenyltransferases journal J. Biol. Chem. volume 271 pages 5289&ndash 92 pmid 8621375 doi 10.1074 jbc.271.10.5289 issue 10 cite journal author Wilson AL, Erdman RA, Castellano F, Maltese WA date Pt 3 title Prenylation of Rab8 GTPase by type I and type II geranylgeranyl transferases journal Biochem. J. volume 333 pages 497&ndash 504 pmid 9677305 pmc 1219609 cite journal author Zhang H, Seabra MC, Deisenhofer J date 2000 title Crystal structure of Rab geranylgeranyltransferase at 2.0 A resolution journal Structure. Fold. Des. volume 8 pages 241&ndash 51 pmid 10745007 doi 10.1016 S0969 2126 00 00102 7 issue 3 cite journal author Thoma NH, Niculae A, Goody RS, Alexandrov K date 2001 title Double prenylation by RabGGTase can proceed without dissociation of the mono prenylated intermediate journal J. Biol. Chem. volume 276 pages 48631&ndash 6 pmid 11591706 doi 10.1074 jbc.M106470200 is ... more details
Drugbox verifiedrevid 415676244 IUPAC name 1 3 R ,5 S 7 chloro 5 2,3 dimethoxyphenyl 1 3 hydroxy 2,2 dimethylpropyl 2 oxo 1,2,3,5 tetrahydro 4,1 benzoxazepin 3 yl acetyl piperidin 4 yl acetic acid image Lapaquistat.svg ChemSpiderID Ref chemspidercite correct chemspider ChemSpiderID 8135996 InChI 1 C31H39ClN2O8 c1 31 2,18 35 17 34 23 9 8 20 32 15 22 23 28 21 6 5 7 24 40 3 29 21 41 4 42 25 30 34 39 16 26 36 33 12 10 19 11 13 33 14 27 37 38 h5 9,15,19,25,28,35H,10 14,16 18H2,1 4H3, H,37,38 t25 ,28 m1 s1 InChIKey HDGUKVZPMPJBFK LEAFIULHBZ smiles O C O CC4CCN C O C C H 1O C H c2cc Cl ccc2N C1 O CC C C CO c3cccc OC c3OC CC4 ChEMBL Ref ebicite correct EBI ChEMBL 341976 StdInChI Ref stdinchicite correct chemspider StdInChI 1S C31H39ClN2O8 c1 31 2,18 35 17 34 23 9 8 20 32 15 22 23 28 21 6 5 7 24 40 3 29 21 41 4 42 25 30 34 39 16 26 36 33 12 10 19 11 13 33 14 27 37 38 h5 9,15,19,25,28,35H,10 14,16 18H2,1 4H3, H,37,38 t25 ,28 m1 s1 StdInChIKey Ref stdinchicite correct chemspider StdInChIKey HDGUKVZPMPJBFK LEAFIULHSA N CAS number 189059 71 0 ATC prefix none ATC suffix ATC supplemental PubChem 9960389 DrugBank C 31 H 39 Cl 1 N 2 O 8 molecular weight 603.103 g mol bioavailability protein bound metabolism elimination half life pregnancy category legal status routes of administration excretion Lapaquistat TAK 475 is a cholesterol lowering drug. Unlike statin s, which inhibit HMG CoA reductase , lapaquistat metabolites inhibit squalene synthase , which is further downstream in the synthesis of cholesterol. It is hoped that side effects can be reduced by not disturbing the mevalonate pathway , which is important for other biochemical molecules besides cholesterol. However, there is increasing evidence that statins which inhibit the mevalonate pathway may be clinically useful because they affect these other molecules including protein prenylation ref name pmid16639429 cite journal author Greenwood J, Steinman L, Zamvil SS title Statin therapy and autoimmune disease from protein prenyl ... more details
Myristoylation is an irreversible, co translational during translation protein modification found in animal s, plant s, fungi and virus es. In this protein modification, a myristoyl group derived from myristic acid is covalent ly attached via an amide bond to the alpha amino group of an N terminal amino acid of a nascent polypeptide . It is more common on glycine residues but also occurs on other amino acids. The modification is catalyzed by the enzyme N myristoyltransferase 1 N myristoyltransferase NMT , and occurs most commonly on glycine residues exposed during co translational N terminal methionine removal. Myristoylation also occurs post translationally, for example when previously internal glycine residues become exposed by caspase cleavage during apoptosis. Function Myristoylation plays a vital role in membrane targeting and signal transduction in plant responses to environmental stress. See also Prenylation Palmitoylation References Podell S and Gribskov M. 2004 Predicting N terminal myristoylation sites in plant proteins , BMC Genomics , 5 , 37. Zha J, Weiler S, Oh KJ, Wei MC, Korsmeyer SJ 2000 Posttranslational N myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis , Science 290 , 1761 1765. External links http www.biomedcentral.com 1471 2164 5 37 B1 Predicting N terminal myristoylation sites in plant proteins Protein posttranslational modification Category Posttranslational modification Category Signal transduction biochem stub de Myristoylierung fr Myristoylation ja ... more details
are essential for the prenylation of Rab G protein Rab proteins. Studies have shown that there is a build up of Prenylation unprenylated Rab27 in lymphoblasts from Choroideremia patients. The link ... more details
author Cates CA, Michael RL, Stayrook KR, et al. title Prenylation of oncogenic human PTP CAAX protein ... MC8 3.0.CO 2 M cite journal author Zeng Q, Si X, Horstmann H, et al. title Prenylation dependent association ... more details
RhoV or Chp or Wrch2 is a small 21 kDa signaling G protein more specifically a GTPase , and is a member of the Rho family of GTPases . Chp was identified in 1998 as a GTPase interacting with the p21 activated kinase PAK2 ref name Aronheim cite journal author Aronheim A, Broder YC, Cohen A, Fritsch A, Belisle B and Abo A. year 1998 title Chp, a homologue of the GTPase Cdc42Hs, activates the JNK pathway and is implicated in reorganizing the actin cytoskeleton journal Curr Biol volume 8 issue 20 pages 1125 8 issn 0960 9822 doi 10.1016 S0960 9822 98 70468 3 pmid 9778532 ref . RhoV Chp delineates with Wrch1 RhoU Wrch a Rho subclass related to Rac GTPase Rac and CDC42 Cdc42 , which emerged in early multicellular organisms during evolution ref name Boureux cite journal author Boureux A, Vignal E, Faure S, Fort P. year 2007 title Evolution of the Rho family of ras like GTPases in eukaryotes journal Mol Biol Evol volume 24 issue 1 pages 203 16 issn 0021 9193 pmid 17449622 doi 10.1128 JB.00142 07 pmc 1913362 ref . RhoV Chp depends on palmitoylation rather than prenylation for association with plasma and intracellular membranes ref name Chenette cite journal author Chenette EJ, Mitin NY and Der CJ. year 2006 title Multiple sequence elements facilitate Chp Rho GTPase subcellular location, membrane association, and transforming activity journal Mol Biol Cell volume 17 issue 7 pages 3108 21 issn 1059 1524 doi 10.1091 mbc.E05 09 0896 pmid 16641371 pmc 1483044 ref . In Xenopus embryos, RhoV is encoded by a canonical Wnt response gene and is induced in the developing neural crest at specification. RhoV activity cooperates with the SNAI1 Snai1 Snail transcription factor for the subsequent induction of the pro invasive transcription factors SNAI2 Snai2 Slug , Sox9 or Twist transcription factor Twist . ref name Guemar cite journal author Guemar L, de Santa Barbara P, Vignal E,Maurel B, Fort P, Faure S. year 2007 title The small GTPase RhoV is an essential regulator of neural crest indu ... more details
Image Mevalonate pathway.png thumb 350px right Mevalonate pathway The mevalonate pathway or HMG CoA reductase pathway or mevalonate dependent MAD route or isoprenoid pathway , is an important cell biology cellular metabolic pathway present in all higher eukaryotes and many bacteria. It is important for the production of dimethylallyl pyrophosphate DMAPP and isopentenyl pyrophosphate IPP , which serve as the basis for the biosynthesis of molecules used in processes as diverse as terpenoid synthesis, protein prenylation , cell membrane maintenance, hormone s, lipid anchored protein protein anchoring , and glycosylation N glycosylation . It is also a part of steroid biosynthesis . Regulation and feedback Several key enzymes can be activated through DNA transcription al regulation on activation of SREBP sterol regulatory element binding protein 1 and 2 . This intracellular sensor detects low cholesterol levels and stimulates endogenous production by the HMG CoA reductase pathway, as well as increasing lipoprotein uptake by up regulating the LDL receptor LDL receptor . Regulation of this pathway is also achieved by controlling the rate of translation of the mRNA, degradation of reductase and phosphorylation. For more information on regulation, see HMG CoA reductase Pharmacology A number of medication drugs target the mevalonate pathway Statin s used to hypercholesterolemia decrease cholesterol levels Bisphosphonate s used to treat various bone degenerative diseases Alternative Plant s and apicomplexa n protozoa such as malaria parasites have the ability to produce their isoprenoids terpenoids using an additional alternative pathway called the methylerythritol phosphate MEP or non mevalonate pathway , which takes place in their plastid s. In addition, most bacteria including important pathogens, such as Mycobacterium tuberculosis , synthesize IPP and DMAPP via the non mevalonate pathway instead. Reactions class wikitable Reaction Diagram Enzyme Acetyl CoA citric acid cycl ... more details
HMBDP as Prenylation prenyl donors . ref name biosynthesis Ildoo Hwang, Hitoshi Sakakibara ... the adenosine as a cytokinin. ref name biosynthesis The prenylation of these adenines is carried ... more details
by a decarboxylation prenylation sequence, reminiscent of the Carroll reaction . Here ... Prenylation journal Org. Lett. volume 9 issue 15 pages 2763 2766 year 2007 doi 10.1021 ol070971k ... more details
science.271.5252.1120 cite journal author Nantais DE, Schwemmle M, Stickney JT, et al. title Prenylation ... 35000617 cite journal author Zeng Q, Si X, Horstmann H, et al. title Prenylation dependent association ... more details
Prenylation of an interferon gamma induced GTP binding protein the human guanylate binding protein ... 35000617 cite journal author Zeng Q, Si X, Horstmann H, et al. title Prenylation dependent association ... more details
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