1pja
From Proteopedia
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|PDB= 1pja |SIZE=350|CAPTION= <scene name='initialview01'>1pja</scene>, resolution 2.7Å | |PDB= 1pja |SIZE=350|CAPTION= <scene name='initialview01'>1pja</scene>, resolution 2.7Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Palmitoyl-protein_hydrolase Palmitoyl-protein hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.22 3.1.2.22] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Palmitoyl-protein_hydrolase Palmitoyl-protein hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.22 3.1.2.22] </span> |
|GENE= PPT2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= PPT2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1ei9|1EI9]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pja OCA], [http://www.ebi.ac.uk/pdbsum/1pja PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pja RCSB]</span> | ||
}} | }} | ||
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[[Category: Nonato, M C.]] | [[Category: Nonato, M C.]] | ||
[[Category: Tandel, S.]] | [[Category: Tandel, S.]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: NAG]] | ||
[[Category: glycoprotein]] | [[Category: glycoprotein]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
[[Category: lysosome]] | [[Category: lysosome]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:00:27 2008'' |
Revision as of 20:00, 30 March 2008
| |||||||
| , resolution 2.7Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | PPT2 (Homo sapiens) | ||||||
| Activity: | Palmitoyl-protein hydrolase, with EC number 3.1.2.22 | ||||||
| Related: | 1EI9
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
The crystal structure of palmitoyl protein thioesterase-2 reveals the basis for divergent substrate specificities of the two lysosomal thioesterases (PPT1 and PPT2)
Overview
Mutations in palmitoyl protein thioesterase-1 (PPT1) have been found to cause the infantile form of neuronal ceroid lipofuscinosis, which is a lysosomal storage disorder characterized by impaired degradation of fatty acid-modified proteins with accumulation of amorphous granular deposits in cortical neurons, leading to mental retardation and death. Palmitoyl protein thioesterase-2 (PPT2) is a second lysosomal hydrolase that shares a 26% identity with PPT1. A previous study had suggested that palmitoyl-CoA was the preferred substrate of PPT2. Furthermore, PPT2 did not hydrolyze palmitate from the several S-palmitoylated protein substrates. Interestingly, PPT2 deficiency in a recent transgenic mouse model is associated with a form of neuronal ceroid lipofuscinosis, suggesting that PPT1 and -2 perform non-redundant roles in lysosomal thioester catabolism. In the current paper, we present the crystal structure of PPT2 at a resolution of 2.7 A. Comparisons of the structures of PPT1 and -2 show very similar architectural features; however, conformational differences in helix alpha4 lead to a solvent-exposed lipid-binding groove in PPT1. The limited space between two parallel loops (beta3-alphaA and beta8-alphaF) located immediately above the lipid-binding groove in PPT2 restricts the binding of fatty acids with bulky head groups, and this binding groove is significantly larger in PPT1. This structural difference accounts for the ability of PPT2 to hydrolyze an unbranched structure such as palmitoyl-CoA but not palmitoylcysteine or palmitoylated proteins. Furthermore, differences in fatty acid chain length specificity of PPT1 and -2, also reported here, are explained by the structure and may provide a biochemical basis for their non-redundant roles.
About this Structure
1PJA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The crystal structure of palmitoyl protein thioesterase-2 (PPT2) reveals the basis for divergent substrate specificities of the two lysosomal thioesterases, PPT1 and PPT2., Calero G, Gupta P, Nonato MC, Tandel S, Biehl ER, Hofmann SL, Clardy J, J Biol Chem. 2003 Sep 26;278(39):37957-64. Epub 2003 Jul 10. PMID:12855696
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