This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2bq8

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:12, 24 July 2019

Crystal structure of human purple acid phosphatase with an inhibitory conformation of the repression loop

Structural highlights

2bq8 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Activity:	Acid phosphatase, with EC number 3.1.3.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[PPA5_HUMAN] Defects in ACP5 are the cause of spondyloenchondrodysplasia with immune dysregulation (SPENCDI) [MIM:607944]. A disease characterized by vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases. The skeletal dysplasia is characterized by radiolucent and irregular spondylar and metaphyseal lesions that represent islands of chondroid tissue within bone. Note=ACP5 inactivating mutations result in a functional excess of phosphorylated osteopontin causing deregulation of osteopontin signaling and consequential autoimmune disease.^[1] ^[2]

Function

[PPA5_HUMAN] Involved in osteopontin/bone sialoprotein dephosphorylation. Its expression seems to increase in certain pathological states such as Gaucher and Hodgkin diseases, the hairy cell, the B-cell, and the T-cell leukemias.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The crystal structure of human purple acid phosphatase recombinantly expressed in Escherichia coli (rHPAP(Ec)) and Pichia pastoris (rHPAP(Pp)) has been determined in two different crystal forms, both at 2.2A resolution. In both cases, the enzyme crystallized in its oxidized (inactive) state, in which both Fe atoms in the dinuclear active site are Fe(III). The main difference between the two structures is the conformation of the enzyme "repression loop". Proteolytic cleavage of this loop in vivo or in vitro results in significant activation of the mammalian PAPs. In the crystals obtained from rHPAP(Ec), the carboxylate side-chain of Asp145 of this loop acts as a bidentate ligand that bridges the two metal atoms, in a manner analogous to a possible binding mode for a phosphate ester substrate in the enzyme-substrate complex. The carboxylate side-chain of Asp145 and the neighboring Phe146 side-chain thus block the active site, thereby inactivating the enzyme. In the crystal structure of rHPAP(Pp), the enzyme "repression loop" has an open conformation similar to that observed in other mammalian PAP structures. The present structures demonstrate that the repression loop exhibits significant conformational flexibility, and the observed alternate binding mode suggests a possible inhibitory role for this loop.

Crystal structures of recombinant human purple Acid phosphatase with and without an inhibitory conformation of the repression loop.,Strater N, Jasper B, Scholte M, Krebs B, Duff AP, Langley DB, Han R, Averill BA, Freeman HC, Guss JM J Mol Biol. 2005 Aug 5;351(1):233-46. Epub 2005 Apr 26. PMID:15993892^[3]

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

References

↑ Briggs TA, Rice GI, Daly S, Urquhart J, Gornall H, Bader-Meunier B, Baskar K, Baskar S, Baudouin V, Beresford MW, Black GC, Dearman RJ, de Zegher F, Foster ES, Frances C, Hayman AR, Hilton E, Job-Deslandre C, Kulkarni ML, Le Merrer M, Linglart A, Lovell SC, Maurer K, Musset L, Navarro V, Picard C, Puel A, Rieux-Laucat F, Roifman CM, Scholl-Burgi S, Smith N, Szynkiewicz M, Wiedeman A, Wouters C, Zeef LA, Casanova JL, Elkon KB, Janckila A, Lebon P, Crow YJ. Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nat Genet. 2011 Feb;43(2):127-31. doi: 10.1038/ng.748. Epub 2011 Jan 9. PMID:21217755 doi:10.1038/ng.748
↑ Lausch E, Janecke A, Bros M, Trojandt S, Alanay Y, De Laet C, Hubner CA, Meinecke P, Nishimura G, Matsuo M, Hirano Y, Tenoutasse S, Kiss A, Rosa RF, Unger SL, Renella R, Bonafe L, Spranger J, Unger S, Zabel B, Superti-Furga A. Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity. Nat Genet. 2011 Feb;43(2):132-7. doi: 10.1038/ng.749. Epub 2011 Jan 9. PMID:21217752 doi:10.1038/ng.749
↑ Strater N, Jasper B, Scholte M, Krebs B, Duff AP, Langley DB, Han R, Averill BA, Freeman HC, Guss JM. Crystal structures of recombinant human purple Acid phosphatase with and without an inhibitory conformation of the repression loop. J Mol Biol. 2005 Aug 5;351(1):233-46. Epub 2005 Apr 26. PMID:15993892 doi:10.1016/j.jmb.2005.04.014

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2bq8"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human purple acid phosphatase with an inhibitory conformation of the repression loop==
-<StructureSection load='2bq8' size='340' side='right' caption='[[2bq8]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+<StructureSection load='2bq8' size='340' side='right'caption='[[2bq8]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2bq8]] is a 1 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=2BQ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BQ8 FirstGlance]. <br>
@@ Line 33: / Line 33: @@
 ==See Also==
-*[[Acid phosphatase|Acid phosphatase]]
+*[[Acid phosphatase 3D structures|Acid phosphatase 3D structures]]
 == References ==
 <references/>
@@ Line 40: / Line 40: @@
 [[Category: Acid phosphatase]]
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Jasper, B]]
 [[Category: Krebs, B]]

2bq8

From Proteopedia

Revision as of 07:12, 24 July 2019

Crystal structure of human purple acid phosphatase with an inhibitory conformation of the repression loop

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox