1z68

From Proteopedia

(Difference between revisions)

Revision as of 07:04, 23 August 2023

Crystal Structure Of Human Fibroblast Activation Protein alpha

Structural highlights

1z68 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 2.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SEPR_HUMAN In association with DPP4 is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May have a role in tissue remodeling during development and wound healing, and may contribute to invasiveness in malignant cancers.^[1]

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

Fibroblast activation protein alpha (FAPalpha) is highly expressed in epithelial cancers and has been implicated in extracellular matrix remodeling, tumor growth, and metastasis. We present the first high resolution structure for the apoenzyme as well as kinetic data toward small dipeptide substrates. FAPalpha exhibits a dipeptidyl peptidase IV (DPPIV)-like fold, featuring an alpha/beta-hydrolase domain and an eight-bladed beta-propeller domain. Known DPPIV dipeptides are cleaved by FAPalpha with an approximately 100-fold decrease in catalytic efficiency compared with DPPIV. Moreover, FAPalpha, but not DPPIV, possesses endopeptidase activity toward N-terminal benzyloxycarbonyl (Z)-blocked peptides. Comparison of the crystal structures of FAPalpha and DPPIV revealed one major difference in the vicinity of the Glu motif (Glu(203)-Glu(204) for FAPalpha; Glu(205)-Glu(206) for DPPIV) within the active site of the enzyme. Ala(657) in FAPalpha, instead of Asp(663) as in DP-PIV, reduces the acidity in this pocket, and this change could explain the lower affinity for N-terminal amines by FAPalpha. This hypothesis was tested by kinetic analysis of the mutant FAPalpha/A657D, which shows on average an approximately 60-fold increase in the catalytic efficiency, as measured by k(cat)/K(m), for the cleavage of dipeptide substrates. Furthermore, the catalytic efficiency of the mutant is reduced by approximately 350-fold for cleavage of Z-Gly-Pro-7-amino-4-methylcoumarin. Our data provide a clear understanding of the molecular determinants responsible for the substrate specificity and endopeptidase activity of FAPalpha.

Structural and kinetic analysis of the substrate specificity of human fibroblast activation protein alpha.,Aertgeerts K, Levin I, Shi L, Snell GP, Jennings A, Prasad GS, Zhang Y, Kraus ML, Salakian S, Sridhar V, Wijnands R, Tennant MG J Biol Chem. 2005 May 20;280(20):19441-4. Epub 2005 Apr 4. PMID:15809306^[2]

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

References

↑ Ghersi G, Zhao Q, Salamone M, Yeh Y, Zucker S, Chen WT. The protease complex consisting of dipeptidyl peptidase IV and seprase plays a role in the migration and invasion of human endothelial cells in collagenous matrices. Cancer Res. 2006 May 1;66(9):4652-61. PMID:16651416 doi:10.1158/0008-5472.CAN-05-1245
↑ Aertgeerts K, Levin I, Shi L, Snell GP, Jennings A, Prasad GS, Zhang Y, Kraus ML, Salakian S, Sridhar V, Wijnands R, Tennant MG. Structural and kinetic analysis of the substrate specificity of human fibroblast activation protein alpha. J Biol Chem. 2005 May 20;280(20):19441-4. Epub 2005 Apr 4. PMID:15809306 doi:10.1074/jbc.C500092200

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/1z68"

@@ Line 3: / Line 3: @@
 <StructureSection load='1z68' size='340' side='right'caption='[[1z68]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1z68]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z68 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z68 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1z68]] 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=1Z68 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z68 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=1z68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z68 OCA], [https://pdbe.org/1z68 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z68 RCSB], [https://www.ebi.ac.uk/pdbsum/1z68 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z68 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/SEPR_HUMAN SEPR_HUMAN]] In association with DPP4 is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May have a role in tissue remodeling during development and wound healing, and may contribute to invasiveness in malignant cancers.<ref>PMID:16651416</ref>
+[https://www.uniprot.org/uniprot/SEPR_HUMAN SEPR_HUMAN] In association with DPP4 is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May have a role in tissue remodeling during development and wound healing, and may contribute to invasiveness in malignant cancers.<ref>PMID:16651416</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 33: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Aertgeerts, K]]
+[[Category: Aertgeerts K]]
-[[Category: Kraus, M L]]
+[[Category: Kraus ML]]
-[[Category: Levin, I]]
+[[Category: Levin I]]
-[[Category: Prasad, G S]]
+[[Category: Prasad GS]]
-[[Category: Salakian, S]]
+[[Category: Salakian S]]
-[[Category: Shi, L]]
+[[Category: Shi L]]
-[[Category: Snell, G P]]
+[[Category: Snell GP]]
-[[Category: Sridhar, V]]
+[[Category: Sridhar V]]
-[[Category: Tennant, M G]]
+[[Category: Tennant MG]]
-[[Category: Wijnands, R]]
+[[Category: Wijnands R]]
-[[Category: Zhang, Y]]
+[[Category: Zhang Y]]
-[[Category: Dipeptidylpeptidase]]
-[[Category: Fapalpha]]
-[[Category: Fibroblast activation protein alpha]]
-[[Category: Integral membrane serine protease]]
-[[Category: Lyase]]
-[[Category: S9b]]
-[[Category: Seprase]]

1z68

From Proteopedia

Revision as of 07:04, 23 August 2023

Crystal Structure Of Human Fibroblast Activation Protein alpha

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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