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3fnm

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Revision as of 06:45, 1 November 2017

Crystal structure of acivicin-inhibited gamma-glutamyltranspeptidase reveals critical roles for its C-terminus in autoprocessing and catalysis

Structural highlights

3fnm is a 4 chain structure with sequence from Atcc 43504. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2nqo, 2qmg
Gene:	HP_1118 (ATCC 43504)
Activity:	Gamma-glutamyltransferase, with EC number 2.3.2.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Helicobacter pylori gamma-glutamyltranspeptidase (HpGT) is a general gamma-glutamyl hydrolase and a demonstrated virulence factor. The enzyme confers a growth advantage to the bacterium, providing essential amino acid precursors by initiating the degradation of extracellular glutathione and glutamine. HpGT is a member of the N-terminal nucleophile (Ntn) hydrolase superfamily and undergoes autoprocessing to generate the active form of the enzyme. Acivicin is a widely used gamma-glutamyltranspeptidase inhibitor that covalently modifies the enzyme, but its precise mechanism of action remains unclear. The time-dependent inactivation of HpGT exhibits a hyperbolic dependence on acivicin concentration with k(max) = 0.033 +/- 0.006 s(-1) and K(I) = 19.7 +/- 7.2 muM. Structure determination of acivicin-modified HpGT (1.7 A; R(factor) = 17.9%; R(free) = 20.8%) demonstrates that acivicin is accommodated within the gamma-glutamyl binding pocket of the enzyme. The hydroxyl group of Thr 380, the catalytic nucleophile in the autoprocessing and enzymatic reactions, displaces chloride from the acivicin ring to form the covalently linked complex. Within the acivicin-modified HpGT structure, the C-terminus of the protein becomes ordered with Phe 567 positioned over the active site. Substitution or deletion of Phe 567 leads to a >10-fold reduction in enzymatic activity, underscoring its importance in catalysis. The mobile C-terminus is positioned by several electrostatic interactions within the C-terminal region, most notably a salt bridge between Arg 475 and Glu 566. Mutational analysis reveals that Arg 475 is critical for the proper placement of the C-terminal region, the Tyr 433 containing loop, and the proposed oxyanion hole.

Crystal Structure of Acivicin-Inhibited gamma-Glutamyltranspeptidase Reveals Critical Roles for Its C-Terminus in Autoprocessing and Catalysis (dagger) (double dagger).,Williams K, Cullati S, Sand A, Biterova EI, Barycki JJ Biochemistry. 2009 Mar 24;48(11):2459-67. PMID:19256527^[1]

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

References

↑ Williams K, Cullati S, Sand A, Biterova EI, Barycki JJ. Crystal Structure of Acivicin-Inhibited gamma-Glutamyltranspeptidase Reveals Critical Roles for Its C-Terminus in Autoprocessing and Catalysis (dagger) (double dagger). Biochemistry. 2009 Mar 24;48(11):2459-67. PMID:19256527 doi:10.1021/bi8014955

1 Structural highlights
2 Evolutionary Conservation
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/3fnm"

@@ Line 1: / Line 1: @@
 ==Crystal structure of acivicin-inhibited gamma-glutamyltranspeptidase reveals critical roles for its C-terminus in autoprocessing and catalysis==
 <StructureSection load='3fnm' size='340' side='right' caption='[[3fnm]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HP_1118 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=210 ATCC 43504])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Gamma-glutamyltransferase Gamma-glutamyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.2 2.3.2.2] </span></td></tr>
-<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=3fnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fnm OCA], [http://pdbe.org/3fnm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fnm RCSB], [http://www.ebi.ac.uk/pdbsum/3fnm PDBsum]</span></td></tr>
+<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=3fnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fnm OCA], [http://pdbe.org/3fnm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fnm RCSB], [http://www.ebi.ac.uk/pdbsum/3fnm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fnm ProSAT]</span></td></tr>
 </table>
 == Evolutionary Conservation ==

3fnm

From Proteopedia

Revision as of 06:45, 1 November 2017

Crystal structure of acivicin-inhibited gamma-glutamyltranspeptidase reveals critical roles for its C-terminus in autoprocessing and catalysis

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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