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4et0

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Revision as of 08:02, 25 December 2014

Crystal structure of circularly permuted human asparaginase-like protein 1

Structural highlights

4et0 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.
Ligands:
Related:	3tkj
Gene:	ASRGL1, ALP, CRASH (Homo sapiens)
Activity:	Asparaginase, with EC number 3.5.1.1
Resources:	FirstGlance, OCA, RCSB, PDBsum

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

The human asparaginase-like protein 1 (hASRGL1) catalyzes the hydrolysis of l-asparagine and isoaspartyl-dipeptides. As an N-terminal nucleophile (Ntn) hydrolase superfamily member, the active form of hASRGL1 is generated by an intramolecular cleavage step with Thr168 as the catalytic residue. However, in vitro, autoprocessing is incomplete ( approximately 50%), fettering the biophysical characterization of hASRGL1. We circumvented this obstacle by constructing a circularly permuted hASRGL1 that uncoupled the autoprocessing reaction, allowing us to kinetically and structurally characterize this enzyme and the precursor-like hASRGL1-Thr168Ala variant. Crystallographic and biochemical evidence suggest an activation mechanism where a torsional restraint on the Thr168 side chain helps drive the intramolecular processing reaction. Cleavage and formation of the active site releases the torsional restriction on Thr168, which is facilitated by a small conserved Gly-rich loop near the active site that allows the conformational changes necessary for activation.

Uncoupling Intramolecular Processing and Substrate Hydrolysis in the N-Terminal Nucleophile Hydrolase hASRGL1 by Circular Permutation.,Li W, Cantor JR, Yogesha SD, Yang S, Chantranupong L, Liu JQ, Agnello G, Georgiou G, Stone EM, Zhang Y ACS Chem Biol. 2012 Aug 29. PMID:22891768^[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
↑ Li W, Cantor JR, Yogesha SD, Yang S, Chantranupong L, Liu JQ, Agnello G, Georgiou G, Stone EM, Zhang Y. Uncoupling Intramolecular Processing and Substrate Hydrolysis in the N-Terminal Nucleophile Hydrolase hASRGL1 by Circular Permutation. ACS Chem Biol. 2012 Aug 29. PMID:22891768 doi:http://dx.doi.org/10.1021/cb300232n

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4et0"

@@ Line 9: / Line 9: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4et0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4et0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4et0 RCSB], [http://www.ebi.ac.uk/pdbsum/4et0 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/ASGL1_HUMAN 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.<ref>PMID:19839645</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4et0

From Proteopedia

Revision as of 08:02, 25 December 2014

Crystal structure of circularly permuted human asparaginase-like protein 1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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