1z68

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[[Image:1z68.gif|left|200px]]<br /><applet load="1z68" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1z68.gif|left|200px]]
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caption="1z68, resolution 2.60&Aring;" />
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'''Crystal Structure Of Human Fibroblast Activation Protein alpha'''<br />
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{{Structure
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|PDB= 1z68 |SIZE=350|CAPTION= <scene name='initialview01'>1z68</scene>, resolution 2.60&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> and <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>
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|ACTIVITY=
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|GENE=
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}}
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'''Crystal Structure Of Human Fibroblast Activation Protein alpha'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1Z68 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=NDG:'>NDG</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z68 OCA].
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1Z68 is a [[Single protein]] structure of sequence from [http://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].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15809306 15809306]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15809306 15809306]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: seprase]]
[[Category: seprase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:12:26 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:31:39 2008''

Revision as of 13:31, 20 March 2008

Image:1z68.gif


PDB ID 1z68

Drag the structure with the mouse to rotate
, resolution 2.60Å
Ligands: and
Coordinates: save as pdb, mmCIF, xml



Crystal Structure Of Human Fibroblast Activation Protein alpha


Overview

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.

About this Structure

1Z68 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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