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.

4pvq

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

Crystal structure of sulfate-bound human l-asparaginase protein

Structural highlights

4pvq is a 2 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 4gdu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.13Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ASGL1_HUMAN Has both L-asparaginase and beta-aspartyl peptidase activity. May be involved in the production of L-aspartate, which can act as an excitatory neurotransmitter in some brain regions. Is highly active with L-Asp beta-methyl ester. Besides, has catalytic activity toward beta-aspartyl dipeptides and their methyl esters, including beta-L-Asp-L-Phe, beta-L-Asp-L-Phe methyl ester (aspartame), beta-L-Asp-L-Ala, beta-L-Asp-L-Leu and beta-L-Asp-L-Lys. Does not have aspartylglucosaminidase activity and is inactive toward GlcNAc-L-Asn. Likewise, has no activity toward glutamine.^[1]

Publication Abstract from PubMed

Asparaginases catalyze the hydrolysis of the amino acid asparagine to aspartate and ammonia. Bacterial asparaginases are used in cancer chemotherapy to deplete asparagine from the blood, because several hematological malignancies depend on extracellular asparagine for growth. To avoid the immune response against the bacterial enzymes, it would be beneficial to replace them with human asparaginases. However, unlike the bacterial asparaginases, the human enzymes have a millimolar K(m) value for asparagine, making them inefficient in depleting the amino acid from blood. To facilitate the development of human variants suitable for therapeutic use, we determined the structure of human l-asparaginase (hASNase3). This asparaginase is an N-terminal nucleophile (Ntn) family member that requires autocleavage between Gly167 and Thr168 to become catalytically competent. For most Ntn hydrolases, this autoproteolytic activation occurs efficiently. In contrast, hASNas3 is relatively stable in its uncleaved state, and this allowed us to observe the structure of the enzyme prior to cleavage. To determine the structure of the cleaved state, we exploited our discovery that the free amino acid glycine promotes complete cleavage of hASNase3. Both enzyme states were elucidated in the absence and presence of the product aspartate. Together, these structures provide insight into the conformational changes required for cleavage and the precise enzyme-substrate interactions. The new understanding of hASNase3 will serve to guide the design of variants that possess a decreased K(m) value for asparagine, making the human enzyme a suitable replacement for the bacterial asparaginases in cancer therapy.

Structures of Apo and Product-Bound Human l-Asparaginase: Insights into the Mechanism of Autoproteolysis and Substrate Hydrolysis.,Nomme J, Su Y, Konrad M, Lavie A Biochemistry. 2012 Aug 28;51(34):6816-26. Epub 2012 Aug 14. PMID:22861376^[2]

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

References

↑ Cantor JR, Stone EM, Chantranupong L, Georgiou G. The human asparaginase-like protein 1 hASRGL1 is an Ntn hydrolase with beta-aspartyl peptidase activity. Biochemistry. 2009 Nov 24;48(46):11026-31. doi: 10.1021/bi901397h. PMID:19839645 doi:10.1021/bi901397h
↑ Nomme J, Su Y, Konrad M, Lavie A. Structures of Apo and Product-Bound Human l-Asparaginase: Insights into the Mechanism of Autoproteolysis and Substrate Hydrolysis. Biochemistry. 2012 Aug 28;51(34):6816-26. Epub 2012 Aug 14. PMID:22861376 doi:http://dx.doi.org/10.1021/bi300870g

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4pvq"

Categories: Homo sapiens | Large Structures | Lavie A | Nomme J

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4pvq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4gdu 4gdu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PVQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PVQ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.13&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4pvq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pvq OCA], [https://pdbe.org/4pvq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pvq RCSB], [https://www.ebi.ac.uk/pdbsum/4pvq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pvq ProSAT]</span></td></tr>
 </table>

4pvq

From Proteopedia

Current revision

Crystal structure of sulfate-bound human l-asparaginase protein

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox