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5m4g

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Revision as of 07:27, 29 November 2017

Crystal Structure of Wild-Type Human Prolidase with Mn ions

Structural highlights

5m4g is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	5m4j, 5m4q, 2okn
Gene:	PEPD, PRD (HUMAN)
Activity:	Xaa-Pro dipeptidase, with EC number 3.4.13.9
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PEPD_HUMAN] Defects in PEPD are a cause of prolidase deficiency (PD) [MIM:170100]. Prolidase deficiency is an autosomal recessive disorder associated with iminodipeptiduria. The clinical phenotype includes skin ulcers, mental retardation, recurrent infections, and a characteristic facies. These features, however are incompletely penetrant and highly variable in both age of onset and severity. There is a tight linkage between the polymorphisms of prolidase and the myotonic dystrophy trait.^[1] ^[2] ^[3] ^[4]

Function

[PEPD_HUMAN] Splits dipeptides with a prolyl or hydroxyprolyl residue in the C-terminal position. Plays an important role in collagen metabolism because the high level of iminoacids in collagen.

Publication Abstract from PubMed

Prolidase is a ubiquitously distributed dipeptidase and the only dipeptidase in humans capable of cleaving the peptide bond preceding the amino acids proline (Pro) or hydroxyproline (Hyp). It is mainly implicated in the degradation of dietary and endogenous proteins. It is also involved in the terminal steps of collagen catabolism by hydrolyzing Pro and Hyp-containing dipeptides. Finally, it is believed to play a role in the regulation of peptidic hormones. Diminished or absent prolidase activity is related to a rare autosomal disease, referred to as prolidase deficiency (PD). This disease manifests itself by a variety of clinical symptoms. To date, there is no definitive cure to PD. This may in part be due to an incomplete understanding of the wild-type (wt) enzyme with respect to substrate-binding mode and consequently the mechanism of the catalyzed reaction. In this work, we describe the high-resolution crystal structures of the wt human prolidase in the ligand-free form as well as in substrate-bound states and in complex with the cleavage product Pro. This series of structures provides much relevant information for the definition of substrate-binding and the reaction mechanism. A recent study on Escherichia coli prolidase revealed how substrates of different length are discriminated. Here, based on our own structural results, we evaluate and extend this analysis. Moreover, we describe and analyze substrate and product binding in the active site and we propose that the crucial catalytic moiety is actually a hydroxide ion. This information significantly advances our understanding of prolidase-based pathologies. DATABASE: The refined structure coordinates as well as the corresponding structure factor amplitudes have been deposited in the PDB under the accession numbers 5M4G, 5M4J, 5M4L, and 5M4Q.

Substrate specificity and reaction mechanism of human prolidase.,Wilk P, Uehlein M, Kalms J, Dobbek H, Mueller U, Weiss MS FEBS J. 2017 Sep;284(17):2870-2885. doi: 10.1111/febs.14158. Epub 2017 Aug 8. PMID:28677335^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Tanoue A, Endo F, Kitano A, Matsuda I. A single nucleotide change in the prolidase gene in fibroblasts from two patients with polypeptide positive prolidase deficiency. Expression of the mutant enzyme in NIH 3T3 cells. J Clin Invest. 1990 Jul;86(1):351-5. PMID:2365824 doi:http://dx.doi.org/10.1172/JCI114708
↑ Ledoux P, Scriver C, Hechtman P. Four novel PEPD alleles causing prolidase deficiency. Am J Hum Genet. 1994 Jun;54(6):1014-21. PMID:8198124
↑ Ledoux P, Scriver CR, Hechtman P. Expression and molecular analysis of mutations in prolidase deficiency. Am J Hum Genet. 1996 Nov;59(5):1035-9. PMID:8900231
↑ Forlino A, Lupi A, Vaghi P, Icaro Cornaglia A, Calligaro A, Campari E, Cetta G. Mutation analysis of five new patients affected by prolidase deficiency: the lack of enzyme activity causes necrosis-like cell death in cultured fibroblasts. Hum Genet. 2002 Oct;111(4-5):314-22. Epub 2002 Aug 14. PMID:12384772 doi:10.1007/s00439-002-0792-5
↑ Wilk P, Uehlein M, Kalms J, Dobbek H, Mueller U, Weiss MS. Substrate specificity and reaction mechanism of human prolidase. FEBS J. 2017 Sep;284(17):2870-2885. doi: 10.1111/febs.14158. Epub 2017 Aug 8. PMID:28677335 doi:http://dx.doi.org/10.1111/febs.14158

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5m4g"

@@ Line 3: / Line 3: @@
 <StructureSection load='5m4g' size='340' side='right' caption='[[5m4g]], [[Resolution|resolution]] 1.48&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5m4g]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M4G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M4G FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5m4g]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5M4G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5M4G FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OH:HYDROXIDE+ION'>OH</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5m4j|5m4j]], [[5m4q|5m4q]], [[2okn|2okn]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PEPD, PRD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Xaa-Pro_dipeptidase Xaa-Pro dipeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.13.9 3.4.13.9] </span></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5m4g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5m4g OCA], [http://pdbe.org/5m4g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5m4g RCSB], [http://www.ebi.ac.uk/pdbsum/5m4g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5m4g ProSAT]</span></td></tr>
@@ Line 25: / Line 27: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Xaa-Pro dipeptidase]]
 [[Category: Dobbek, H]]

5m4g

From Proteopedia

Revision as of 07:27, 29 November 2017

Crystal Structure of Wild-Type Human Prolidase with Mn ions

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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