1yt4

From Proteopedia

(Difference between revisions)

Revision as of 08:52, 20 January 2021

Crystal structure of TEM-76 beta-lactamase at 1.4 Angstrom resolution

Structural highlights

1yt4 is a 1 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1jwp, 1li0, 1tdl
Gene:	bla ("Bacillus coli" Migula 1895)
Activity:	Beta-lactamase, with EC number 3.5.2.6
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BLAT_ECOLX] TEM-type are the most prevalent beta-lactamases in enterobacteria; they hydrolyze the beta-lactam bond in susceptible beta-lactam antibiotics, thus conferring resistance to penicillins and cephalosporins. TEM-3 and TEM-4 are capable of hydrolyzing cefotaxime and ceftazidime. TEM-5 is capable of hydrolyzing ceftazidime. TEM-6 is capable of hydrolyzing ceftazidime and aztreonam. TEM-8/CAZ-2, TEM-16/CAZ-7 and TEM-24/CAZ-6 are markedly active against ceftazidime. IRT-4 shows resistance to beta-lactamase inhibitors.

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

Beta-lactamase confers resistance to penicillin-like antibiotics by hydrolyzing their beta-lactam bond. To combat these enzymes, inhibitors covalently cross-linking the hydrolytic Ser70 to Ser130 were introduced. In turn, mutant beta-lactamases have emerged with decreased susceptibility to these mechanism-based inhibitors. Substituting Ser130 with glycine in the inhibitor-resistant TEM (IRT) mutant TEM-76 (S130G) prevents the irreversible cross-linking step. Since the completely conserved Ser130 is thought to transfer a proton important for catalysis, its substitution might be hypothesized to result in a nonfunctional enzyme; this is clearly not the case. To investigate how TEM-76 remains active, its structure was determined by X-ray crystallography to 1.40 A resolution. A new water molecule (Wat1023) is observed in the active site, with two configurations located 1.1 and 1.3 A from the missing Ser130 Ogamma; this water molecule likely replaces the Ser130 side-chain hydroxyl in substrate hydrolysis. Intriguingly, this same water molecule is seen in the IRT TEM-32 (M69I/M182T), where Ser130 has moved significantly. TEM-76 shares other structural similarities with various IRTs; like TEM-30 (R244S) and TEM-84 (N276D), the water molecule activating clavulanate for cross-linking (Wat1614) is disordered (in TEM-30 it is actually absent). As expected, TEM-76 has decreased kinetic activity, likely due to the replacement of the Ser130 side-chain hydroxyl with a water molecule. In contrast to the recently determined structure of the S130G mutant in the related SHV-1 beta-lactamase, in TEM-76 the key hydrolytic water (Wat1561) is still present. The conservation of similar accommodations among IRT mutants suggests that resistance arises from common mechanisms, despite the disparate locations of the various substitutions.

Structural consequences of the inhibitor-resistant Ser130Gly substitution in TEM beta-lactamase.,Thomas VL, Golemi-Kotra D, Kim C, Vakulenko SB, Mobashery S, Shoichet BK Biochemistry. 2005 Jul 5;44(26):9330-8. PMID:15981999^[1]

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

References

↑ Thomas VL, Golemi-Kotra D, Kim C, Vakulenko SB, Mobashery S, Shoichet BK. Structural consequences of the inhibitor-resistant Ser130Gly substitution in TEM beta-lactamase. Biochemistry. 2005 Jul 5;44(26):9330-8. PMID:15981999 doi:http://dx.doi.org/10.1021/bi0502700

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/1yt4"

@@ Line 1: / Line 1: @@
 ==Crystal structure of TEM-76 beta-lactamase at 1.4 Angstrom resolution==
-<StructureSection load='1yt4' size='340' side='right' caption='[[1yt4]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
+<StructureSection load='1yt4' size='340' side='right'caption='[[1yt4]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1yt4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YT4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YT4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1yt4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YT4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1YT4 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1jwp|1jwp]], [[1li0|1li0]], [[1tdl|1tdl]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1jwp|1jwp]], [[1li0|1li0]], [[1tdl|1tdl]]</div></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </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=1yt4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yt4 OCA], [http://pdbe.org/1yt4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yt4 RCSB], [http://www.ebi.ac.uk/pdbsum/1yt4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yt4 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1yt4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yt4 OCA], [http://pdbe.org/1yt4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yt4 RCSB], [http://www.ebi.ac.uk/pdbsum/1yt4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yt4 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 32: / Line 32: @@
 ==See Also==
-*[[Beta-lactamase|Beta-lactamase]]
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
 == References ==
 <references/>
@@ Line 39: / Line 39: @@
 [[Category: Bacillus coli migula 1895]]
 [[Category: Beta-lactamase]]
+[[Category: Large Structures]]
 [[Category: Golemi-Kotra, D]]
 [[Category: Kim, C]]

1yt4

From Proteopedia

Revision as of 08:52, 20 January 2021

Crystal structure of TEM-76 beta-lactamase at 1.4 Angstrom resolution

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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