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7fh3

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Current revision

Crystal structure of the ATP sulfurylase domain of human PAPSS2

Structural highlights

7fh3 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

PAPS2_HUMAN Defects in PAPSS2 are the cause of spondyloepimetaphyseal dysplasia Pakistani type (SEMD-PA) [MIM:612847. A bone disease characterized by epiphyseal dysplasia with mild metaphyseal abnormalities. Clinical features include short stature evidenced at birth, short and bowed lower limbs, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints. Some patients may manifest premature pubarche and hyperandrogenism associated with skeletal dysplasia and short stature.^[1] ^[2]

Function

PAPS2_HUMAN Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5'-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3'-phosphoadenylylsulfate (PAPS: activated sulfate donor used by sulfotransferase). In mammals, PAPS is the sole source of sulfate; APS appears to be only an intermediate in the sulfate-activation pathway. May have a important role in skeletogenesis during postnatal growth (By similarity).

Publication Abstract from PubMed

Sulfation is an essential modification on biomolecules in living cells, and 3'-Phosphoadenosine-5'-phosphosulfate (PAPS) is its unique and universal sulfate donor. Human PAPS synthases (PAPSS1 and 2) are the only enzymes that catalyze PAPS production from inorganic sulfate. Unexpectedly, PAPSS1 and PAPSS2 do not functional complement with each other, and abnormal function of PAPSS2 but not PAPSS1 leads to numerous human diseases including bone development diseases, hormone disorder and cancers. Here, we reported the crystal structures of ATP-sulfurylase domain of human PAPSS2 (ATPS2) and ATPS2 in complex with is product 5'-phosphosulfate (APS). We demonstrated that ATPS2 recognizes the substrates by using family conserved residues located on the HXXH and PP motifs, and achieves substrate binding and releasing by employing a non-conserved phenylalanine (Phe550) through a never observed flipping mechanism. Our discovery provides additional information to better understand the biological function of PAPSS2 especially in tumorigenesis, and may facilitate the drug discovery against this enzyme.

Structural basis for the substrate recognition mechanism of ATP-sulfurylase domain of human PAPS synthase 2.,Zhang P, Zhang L, Hou Z, Lin H, Gao H, Zhang L Biochem Biophys Res Commun. 2022 Jan 1;586:1-7. doi: 10.1016/j.bbrc.2021.11.062. , Epub 2021 Nov 19. PMID:34818583^[3]

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

References

↑ Noordam C, Dhir V, McNelis JC, Schlereth F, Hanley NA, Krone N, Smeitink JA, Smeets R, Sweep FC, Claahsen-van der Grinten HL, Arlt W. Inactivating PAPSS2 mutations in a patient with premature pubarche. N Engl J Med. 2009 May 28;360(22):2310-8. doi: 10.1056/NEJMoa0810489. PMID:19474428 doi:10.1056/NEJMoa0810489
↑ Ahmad M, Faiyaz Ul Haque M, Ahmad W, Abbas H, Haque S, Krakow D, Rimoin DL, Lachman RS, Cohn DH. Distinct, autosomal recessive form of spondyloepimetaphyseal dysplasia segregating in an inbred Pakistani kindred. Am J Med Genet. 1998 Aug 6;78(5):468-73. PMID:9714015
↑ Zhang P, Zhang L, Hou Z, Lin H, Gao H, Zhang L. Structural basis for the substrate recognition mechanism of ATP-sulfurylase domain of human PAPS synthase 2. Biochem Biophys Res Commun. 2022 Jan 1;586:1-7. doi: 10.1016/j.bbrc.2021.11.062. , Epub 2021 Nov 19. PMID:34818583 doi:http://dx.doi.org/10.1016/j.bbrc.2021.11.062

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/7fh3"

Categories: Homo sapiens | Large Structures | Zhang L | Zhang P

@@ Line 3: / Line 3: @@
 <StructureSection load='7fh3' size='340' side='right'caption='[[7fh3]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7fh3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FH3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FH3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7fh3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FH3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FH3 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7fh3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fh3 OCA], [https://pdbe.org/7fh3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fh3 RCSB], [https://www.ebi.ac.uk/pdbsum/7fh3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fh3 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/PAPS2_HUMAN PAPS2_HUMAN]] Defects in PAPSS2 are the cause of spondyloepimetaphyseal dysplasia Pakistani type (SEMD-PA) [MIM:[https://omim.org/entry/612847 612847]]. A bone disease characterized by epiphyseal dysplasia with mild metaphyseal abnormalities. Clinical features include short stature evidenced at birth, short and bowed lower limbs, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints. Some patients may manifest premature pubarche and hyperandrogenism associated with skeletal dysplasia and short stature.<ref>PMID:19474428</ref> <ref>PMID:9714015</ref>
+[https://www.uniprot.org/uniprot/PAPS2_HUMAN PAPS2_HUMAN] Defects in PAPSS2 are the cause of spondyloepimetaphyseal dysplasia Pakistani type (SEMD-PA) [MIM:[https://omim.org/entry/612847 612847]. A bone disease characterized by epiphyseal dysplasia with mild metaphyseal abnormalities. Clinical features include short stature evidenced at birth, short and bowed lower limbs, mild brachydactyly, kyphoscoliosis, abnormal gait, enlarged knee joints. Some patients may manifest premature pubarche and hyperandrogenism associated with skeletal dysplasia and short stature.<ref>PMID:19474428</ref> <ref>PMID:9714015</ref>
 == Function ==
-[[https://www.uniprot.org/uniprot/PAPS2_HUMAN PAPS2_HUMAN]] Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5'-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3'-phosphoadenylylsulfate (PAPS: activated sulfate donor used by sulfotransferase). In mammals, PAPS is the sole source of sulfate; APS appears to be only an intermediate in the sulfate-activation pathway. May have a important role in skeletogenesis during postnatal growth (By similarity).
+[https://www.uniprot.org/uniprot/PAPS2_HUMAN PAPS2_HUMAN] Bifunctional enzyme with both ATP sulfurylase and APS kinase activity, which mediates two steps in the sulfate activation pathway. The first step is the transfer of a sulfate group to ATP to yield adenosine 5'-phosphosulfate (APS), and the second step is the transfer of a phosphate group from ATP to APS yielding 3'-phosphoadenylylsulfate (PAPS: activated sulfate donor used by sulfotransferase). In mammals, PAPS is the sole source of sulfate; APS appears to be only an intermediate in the sulfate-activation pathway. May have a important role in skeletogenesis during postnatal growth (By similarity).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Zhang, L]]
+[[Category: Zhang L]]
-[[Category: Zhang, P]]
+[[Category: Zhang P]]
-[[Category: Atp sulfurylase]]
-[[Category: Biosynthetic protein]]

7fh3

From Proteopedia

Current revision

Crystal structure of the ATP sulfurylase domain of human PAPSS2

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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