2b3v: Difference between revisions
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|GENE= SAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= SAT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=COG0456 RimI], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam00583 Acetyltransf_1]</span> | |DOMAIN=<span class='plainlinks'>[http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=COG0456 RimI], [http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam00583 Acetyltransf_1]</span> | ||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2b3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b3v OCA], [http://www.ebi.ac.uk/pdbsum/2b3v PDBsum | |RELATEDENTRY=[[2b3u|2B3U]] | ||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2b3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b3v OCA], [http://www.ebi.ac.uk/pdbsum/2b3v PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2b3v RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
Spermidine/spermine N1-acetyltransferase (SSAT) is a key enzyme in the control of polyamine levels in human cells, as acetylation of spermidine and spermine triggers export or degradation. Increased intracellular polyamine levels accompany several types of cancers as well as other human diseases, and compounds that affect the expression, activity, or stability of SSAT are being explored as potential therapeutic drugs. We have expressed human SSAT from the cloned cDNA in Escherichia coli and have determined high-resolution structures of wild-type and mutant SSAT, as the free dimer and in binary and ternary complexes with CoA, acetyl-CoA (AcCoA), spermine, and the inhibitor N1,N11bis-(ethyl)-norspermine (BE-3-3-3). These structures show details of binding sites for cofactor, substrates, and inhibitor and provide a framework to understand enzymatic activity, mutations, and the action of potential drugs. Two dimer conformations were observed: a symmetric form with two open surface channels capable of binding substrate or cofactor, and an asymmetric form in which only one of the surface channels appears capable of binding and acetylating polyamines. SSAT was found to self-acetylate lysine-26 in the presence of AcCoA and absence of substrate, a reaction apparently catalzyed by AcCoA bound in the second channel of the asymmetric dimer. These unexpected and intriguing complexities seem likely to have some as yet undefined role in regulating SSAT activity or stability as a part of polyamine homeostasis. Sequence signatures group SSAT with proteins that appear to have thialysine Nepsilon-acetyltransferase activity. | Spermidine/spermine N1-acetyltransferase (SSAT) is a key enzyme in the control of polyamine levels in human cells, as acetylation of spermidine and spermine triggers export or degradation. Increased intracellular polyamine levels accompany several types of cancers as well as other human diseases, and compounds that affect the expression, activity, or stability of SSAT are being explored as potential therapeutic drugs. We have expressed human SSAT from the cloned cDNA in Escherichia coli and have determined high-resolution structures of wild-type and mutant SSAT, as the free dimer and in binary and ternary complexes with CoA, acetyl-CoA (AcCoA), spermine, and the inhibitor N1,N11bis-(ethyl)-norspermine (BE-3-3-3). These structures show details of binding sites for cofactor, substrates, and inhibitor and provide a framework to understand enzymatic activity, mutations, and the action of potential drugs. Two dimer conformations were observed: a symmetric form with two open surface channels capable of binding substrate or cofactor, and an asymmetric form in which only one of the surface channels appears capable of binding and acetylating polyamines. SSAT was found to self-acetylate lysine-26 in the presence of AcCoA and absence of substrate, a reaction apparently catalzyed by AcCoA bound in the second channel of the asymmetric dimer. These unexpected and intriguing complexities seem likely to have some as yet undefined role in regulating SSAT activity or stability as a part of polyamine homeostasis. Sequence signatures group SSAT with proteins that appear to have thialysine Nepsilon-acetyltransferase activity. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: structural genomic]] | [[Category: structural genomic]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:01:06 2008'' | ||
Revision as of 02:01, 31 March 2008
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| , resolution 1.95Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | SAT (Homo sapiens) | ||||||
| Activity: | Diamine N-acetyltransferase, with EC number 2.3.1.57 | ||||||
| Domains: | RimI, Acetyltransf_1 | ||||||
| Related: | 2B3U
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Spermine spermidine acetyltransferase in complex with acetylcoa, K26R mutant
OverviewOverview
Spermidine/spermine N1-acetyltransferase (SSAT) is a key enzyme in the control of polyamine levels in human cells, as acetylation of spermidine and spermine triggers export or degradation. Increased intracellular polyamine levels accompany several types of cancers as well as other human diseases, and compounds that affect the expression, activity, or stability of SSAT are being explored as potential therapeutic drugs. We have expressed human SSAT from the cloned cDNA in Escherichia coli and have determined high-resolution structures of wild-type and mutant SSAT, as the free dimer and in binary and ternary complexes with CoA, acetyl-CoA (AcCoA), spermine, and the inhibitor N1,N11bis-(ethyl)-norspermine (BE-3-3-3). These structures show details of binding sites for cofactor, substrates, and inhibitor and provide a framework to understand enzymatic activity, mutations, and the action of potential drugs. Two dimer conformations were observed: a symmetric form with two open surface channels capable of binding substrate or cofactor, and an asymmetric form in which only one of the surface channels appears capable of binding and acetylating polyamines. SSAT was found to self-acetylate lysine-26 in the presence of AcCoA and absence of substrate, a reaction apparently catalzyed by AcCoA bound in the second channel of the asymmetric dimer. These unexpected and intriguing complexities seem likely to have some as yet undefined role in regulating SSAT activity or stability as a part of polyamine homeostasis. Sequence signatures group SSAT with proteins that appear to have thialysine Nepsilon-acetyltransferase activity.
About this StructureAbout this Structure
2B3V is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Structures of wild-type and mutant human spermidine/spermine N1-acetyltransferase, a potential therapeutic drug target., Bewley MC, Graziano V, Jiang J, Matz E, Studier FW, Pegg AE, Coleman CS, Flanagan JM, Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2063-8. Epub 2006 Feb 2. PMID:16455797
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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Diamine N-acetyltransferase
- Homo sapiens
- Single protein
- Bewley, M C.
- Coleman, C S.
- Flanagan, J M.
- Graziano, V.
- Jiang, J S.
- Matz, E.
- NYSGXRC, New York Structural GenomiX Research Consortium.
- Pegg, A P.
- Studier, F W.
- New york structural genomix research consortium
- Nysgxrc
- Polyamine
- Protein structure initiative
- Psi
- Structural genomic