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.

1pw8

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 06:57, 24 July 2019

Covalent Acyl Enzyme Complex Of The R61 DD-Peptidase with A Highly Specific Cephalosporin

Structural highlights

1pw8 is a 1 chain structure with sequence from Streptomyces sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1mpl, 1ikg, 1iki
Activity:	Serine-type D-Ala-D-Ala carboxypeptidase, with EC number 3.4.16.4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DAC_STRSR] Catalyzes distinct carboxypeptidation and transpeptidation reactions during the last stages of wall peptidoglycan synthesis. Mistaking a beta-lactam antibiotic molecule for a normal substrate (i.e. a D-alanyl-D-alanine-terminated peptide), it becomes immobilized in the form of a long-lived, serine-ester-linked acyl enzyme and thus behave as penicillin-binding protein (PBP).

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

The bacterial D-alanyl-D-alanine transpeptidases (DD-peptidases) are the killing targets of beta-lactams, the most important clinical defense against bacterial infections. However, due to the constant development of antibiotic-resistance mechanisms by bacteria, there is an ever-present need for new, more effective antimicrobial drugs. While enormous numbers of beta-lactam compounds have been tested for antibiotic activity in over 50 years of research, the success of a beta-lactam structure in terms of antibiotic activity remains unpredictable. Tipper and Strominger suggested long ago that beta-lactams inhibit DD-peptidases because they mimic the D-alanyl-D-alanine motif of the peptidoglycan substrate of these enzymes. They also predicted that beta-lactams having a peptidoglycan-mimetic side-chain might be better antibiotics than their non-specific counterparts, but decades of research have not provided any evidence for this. We have recently described two such novel beta-lactams. The first is a penicillin having the glycyl-L-alpha-amino-epsilon-pimelyl side-chain of Streptomyces strain R61 peptidoglycan, making it the "perfect penicillin" for this organism. The other is a cephalosporin with the same side-chain. Here, we describe the X-ray crystal structures of the perfect penicillin in non-covalent and covalent complexes with the Streptomyces R61 DD-peptidase. The structure of the non-covalent enzyme-inhibitor complex is the first such complex to be trapped crystallographically with a DD-peptidase. In addition, the covalent complex of the peptidyl-cephalosporin with the R61 DD-peptidase is described. Finally, two covalent complexes with the traditional beta-lactams benzylpenicillin and cephalosporin C were determined for comparison with the peptidyl beta-lactams. These structures, together with relevant kinetics data, support Tipper and Strominger's assertion that peptidoglycan-mimetic side-chains should improve beta-lactams as inhibitors of DD-peptidases.

Crystal structures of complexes between the R61 DD-peptidase and peptidoglycan-mimetic beta-lactams: a non-covalent complex with a "perfect penicillin".,Silvaggi NR, Josephine HR, Kuzin AP, Nagarajan R, Pratt RF, Kelly JA J Mol Biol. 2005 Jan 21;345(3):521-33. PMID:15581896^[1]

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

References

↑ Silvaggi NR, Josephine HR, Kuzin AP, Nagarajan R, Pratt RF, Kelly JA. Crystal structures of complexes between the R61 DD-peptidase and peptidoglycan-mimetic beta-lactams: a non-covalent complex with a "perfect penicillin". J Mol Biol. 2005 Jan 21;345(3):521-33. PMID:15581896 doi:http://dx.doi.org/10.1016/j.jmb.2004.10.076

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1pw8"

@@ Line 1: / Line 1: @@
 ==Covalent Acyl Enzyme Complex Of The R61 DD-Peptidase with A Highly Specific Cephalosporin==
-<StructureSection load='1pw8' size='340' side='right' caption='[[1pw8]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
+<StructureSection load='1pw8' size='340' side='right'caption='[[1pw8]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1pw8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptomyces_sp. Streptomyces sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PW8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PW8 FirstGlance]. <br>
@@ Line 30: / Line 30: @@
 </div>
 <div class="pdbe-citations 1pw8" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Serine-type D-Ala-D-Ala carboxypeptidase]]
 [[Category: Streptomyces sp]]

1pw8

From Proteopedia

Revision as of 06:57, 24 July 2019

Covalent Acyl Enzyme Complex Of The R61 DD-Peptidase with A Highly Specific Cephalosporin

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox