View source for 4upk


==Phosphonate monoester hydrolase SpPMH from Silicibacter pomeroyi==
<StructureSection load='4upk' size='340' side='right'caption='[[4upk]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4upk]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Ruegeria_pomeroyi_DSS-3 Ruegeria pomeroyi DSS-3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UPK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UPK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.24&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4upk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4upk OCA], [https://pdbe.org/4upk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4upk RCSB], [https://www.ebi.ac.uk/pdbsum/4upk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4upk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q5LKJ1_RUEPO Q5LKJ1_RUEPO] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Highly proficient, promiscuous enzymes can be springboards for functional evolution, able to avoid loss of function during adaptation by their capacity to promote multiple reactions. We employ systematic comparative study of structure, sequence and substrate specificity to track the evolution of specificity and reactivity between promiscuous members of clades of the alkaline phosphatase (AP) superfamily. Construction of a phylogenetic tree of protein sequences maps out the likely transition zone between arylsulfatases (ASs) and phosphonate monoester hydrolases (PMHs). Kinetic analysis shows that all enzymes characterized have four chemically distinct phospho- and sulfoesterase activities, with rate accelerations ranging from 1011-1017-fold for their primary and 109-1012-fold for their promiscuous reactions, suggesting that catalytic promiscuity is widespread in the AP-superfamily. This functional characterization and crystallography reveal a novel class of ASs that is so similar in sequence to known PMHs that it had not been recognized as having diverged in function. Based on analysis of snapshots of catalytic promiscuity 'in transition' we develop possible models that would allow functional evolution and determine scenarios for trade-off between multiple activities. For the new ASs we observe largely invariant substrate specificity that would facilitate the transition from ASs to PMHs via trade-off-free molecular exaptation, i.e. evolution without initial loss of primary activity and specificity toward the original substrate. This ability to bypass low activity generalists provides a molecular solution to avoid adaptive conflict.

Balancing Specificity and Promiscuity in Enzyme Evolution: Multidimensional Activity Transitions in the Alkaline Phosphatase Superfamily.,van Loo B, Bayer CD, Fischer G, Jonas S, Valkov E, Mohamed MF, Vorobieva A, Dutruel C, Hyvonen M, Hollfelder F J Am Chem Soc. 2018 Nov 30. doi: 10.1021/jacs.8b10290. PMID:30497259<ref>PMID:30497259</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4upk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Ruegeria pomeroyi DSS-3]]
[[Category: Hollfelder F]]
[[Category: Hyvonen M]]
[[Category: Valkov E]]
[[Category: Van Loo B]]