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3ic1

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Revision as of 07:40, 24 December 2014

Crystal structure of zinc-bound succinyl-diaminopimelate desuccinylase from Haemophilus influenzae

Structural highlights

3ic1 is a 2 chain structure with sequence from Haemophilus influenzae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	dapE, HI0102 (Haemophilus influenzae)
Activity:	Succinyl-diaminopimelate desuccinylase, with EC number 3.5.1.18
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[DAPE_HAEIN] Catalyzes the hydrolysis of N-succinyl-L,L-diaminopimelic acid (SDAP), forming succinate and LL-2,6-diaminoheptanedioate (DAP), an intermediate involved in the bacterial biosynthesis of lysine and meso-diaminopimelic acid, an essential component of bacterial cell walls. It can only hydrolyze L,L-N-succinyl-diaminopimelic acid (L,L-SDAP) and is inactive toward D,L-, L,D-, and D,D-SDAP.^[1] ^[2] ^[3]

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

Biosynthesis of lysine and meso-diaminopimelic acid in bacteria provides essential components for protein synthesis and construction of the bacterial peptidoglycan cell wall. The dapE operon enzymes synthesize both meso-diaminopimelic acid and lysine and, therefore, represent potential targets for novel antibacterials. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase functions in a late step of the pathway and converts N-succinyl-L,L-diaminopimelic acid to L,L-diaminopimelic acid and succinate. Deletion of the dapE gene is lethal to Helicobacter pylori and Mycobacterium smegmatis, indicating that DapE's are essential for cell growth and proliferation. Since there are no similar pathways in humans, inhibitors that target DapE may have selective toxicity against only bacteria. A major limitation in developing antimicrobial agents that target DapE has been the lack of structural information. Herein, we report the high-resolution X-ray crystal structures of the DapE from Haemophilus influenzae with one and two zinc ions bound in the active site, respectively. These two forms show different activity. Based on these newly determined structures, we propose a revised catalytic mechanism of peptide bond cleavage by DapE enzymes. These structures provide important insight into catalytic mechanism of DapE enzymes as well as a structural foundation that is critical for the rational design of DapE inhibitors.

Structural basis for catalysis by the mono- and dimetalated forms of the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase.,Nocek BP, Gillner DM, Fan Y, Holz RC, Joachimiak A J Mol Biol. 2010 Apr 2;397(3):617-26. Epub 2010 Feb 4. PMID:20138056^[4]

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

References

↑ Bienvenue DL, Gilner DM, Davis RS, Bennett B, Holz RC. Substrate specificity, metal binding properties, and spectroscopic characterization of the DapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Haemophilus influenzae. Biochemistry. 2003 Sep 16;42(36):10756-63. PMID:12962500 doi:http://dx.doi.org/10.1021/bi034845+
↑ Davis R, Bienvenue D, Swierczek SI, Gilner DM, Rajagopal L, Bennett B, Holz RC. Kinetic and spectroscopic characterization of the E134A- and E134D-altered dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Haemophilus influenzae. J Biol Inorg Chem. 2006 Mar;11(2):206-16. Epub 2006 Jan 19. PMID:16421726 doi:10.1007/s00775-005-0071-8
↑ Gillner DM, Bienvenue DL, Nocek BP, Joachimiak A, Zachary V, Bennett B, Holz RC. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Haemophilus influenzae contains two active-site histidine residues. J Biol Inorg Chem. 2009 Jan;14(1):1-10. doi: 10.1007/s00775-008-0418-z. Epub 2008, Aug 19. PMID:18712420 doi:10.1007/s00775-008-0418-z
↑ Nocek BP, Gillner DM, Fan Y, Holz RC, Joachimiak A. Structural basis for catalysis by the mono- and dimetalated forms of the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase. J Mol Biol. 2010 Apr 2;397(3):617-26. Epub 2010 Feb 4. PMID:20138056 doi:10.1016/j.jmb.2010.01.062

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/3ic1"

@@ Line 8: / Line 8: @@
 <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=3ic1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ic1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ic1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ic1 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/DAPE_HAEIN DAPE_HAEIN]] Catalyzes the hydrolysis of N-succinyl-L,L-diaminopimelic acid (SDAP), forming succinate and LL-2,6-diaminoheptanedioate (DAP), an intermediate involved in the bacterial biosynthesis of lysine and meso-diaminopimelic acid, an essential component of bacterial cell walls. It can only hydrolyze L,L-N-succinyl-diaminopimelic acid (L,L-SDAP) and is inactive toward D,L-, L,D-, and D,D-SDAP.<ref>PMID:12962500</ref> <ref>PMID:16421726</ref> <ref>PMID:18712420</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3ic1

From Proteopedia

Revision as of 07:40, 24 December 2014

Crystal structure of zinc-bound succinyl-diaminopimelate desuccinylase from Haemophilus influenzae

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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