View source for 4gvr


==X-ray structure of the Archaeoglobus fulgidus methenyl-tetrahydromethanopterin cyclohydrolase==
<StructureSection load='4gvr' size='340' side='right'caption='[[4gvr]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4gvr]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Archaeoglobus_fulgidus_DSM_4304 Archaeoglobus fulgidus DSM 4304]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GVR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GVR 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]] 1.52&#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=4gvr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gvr OCA], [https://pdbe.org/4gvr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gvr RCSB], [https://www.ebi.ac.uk/pdbsum/4gvr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gvr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MCH_ARCFU MCH_ARCFU] Catalyzes the hydrolysis of methenyl-H(4)MPT(+) to 5-formyl-H(4)MPT.
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== Publication Abstract from PubMed ==
Methenyltetrahydromethanopterin (methenyl-H(4)MPT(+)) cyclohydrolase (Mch) catalyzes the interconversion of methenyl-H(4)MPT(+) and formyl-H(4)MPT in the one-carbon energy metabolism of methanogenic, methanotrophic, and sulfate-reducing archaea and of methylotrophic bacteria. To understand the catalytic mechanism of this reaction, we kinetically characterized site-specific variants of Mch from Archaeoglobus fulgidus (aMch) and determined the X-ray structures of the substrate-free aMch(E186Q), the aMch:H(4)MPT complex, and the aMch(E186Q):formyl-H(4)MPT complex. (Formyl-)H(4)MPT is embedded inside a largely preformed, interdomain pocket of the homotrimeric enzyme with the pterin and benzyl rings being oriented nearly perpendicular to each other. The active site is primarily built up by the segment 93:95, Arg183 and Glu186 that either interact with the catalytic water attacking methenyl-H(4)MPT(+) or with the formyl oxygen of formyl-H(4)MPT. The catalytic function of the strictly conserved Arg183 and Glu186 was substantiated by the low enzymatic activities of the E186A, E186D, E186N, E186Q, R183A, R183Q, R183E, R183K, and R183E-E186Q variants. Glu186 most likely acts as a general base. Arg183 decisively influences the pK(a) value of Glu186 and the proposed catalytic water mainly by its positive charge. In addition, Glu186 appears to be also responsible for product specificity by donating a proton to the directly neighbored N(10) tertiary amine of H(4)MPT. Thus, N(10) becomes a better leaving group than N(5) which implies the generation of N(5)-formyl-H(4)MPT. For comparison, methenyltetrahydrofolate (H(4)F) cyclohydrolase produces N(10)-formyl-H(4)F in an analogous reaction. An enzymatic mechanism of Mch is postulated and compared with that of other cyclohydrolases.

Structure and catalytic mechanism of N(5),N(10)-methenyl-tetrahydromethanopterin cyclohydrolase.,Upadhyay V, Demmer U, Warkentin E, Moll J, Shima S, Ermler U Biochemistry. 2012 Oct 23;51(42):8435-43. doi: 10.1021/bi300777k. Epub 2012 Oct, 8. PMID:23013430<ref>PMID:23013430</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Cyclohydrolase 3D structures|Cyclohydrolase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Archaeoglobus fulgidus DSM 4304]]
[[Category: Large Structures]]
[[Category: Demmer U]]
[[Category: Ermler U]]
[[Category: Moll J]]
[[Category: Shima S]]
[[Category: Upadhyay V]]
[[Category: Warkentin E]]