View source for 5amm


==Structure of Leishmania major peroxidase D211N mutant==
<StructureSection load='5amm' size='340' side='right'caption='[[5amm]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5amm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_major Leishmania major]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AMM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AMM 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]] 2.09&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></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=5amm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5amm OCA], [https://pdbe.org/5amm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5amm RCSB], [https://www.ebi.ac.uk/pdbsum/5amm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5amm ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q4Q3K2_LEIMA Q4Q3K2_LEIMA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Leishmania major, the parasitic causative agent of leishmaniasis, produces a heme peroxidase (LmP), which catalyzes the peroxidation of mitochondrial cytochrome c (LmCytc) for protection from reactive oxygen species produced by the host. The association of LmP and LmCytc, which is known from kinetics measurements to be very fast ( approximately 108 M-1 s-1), does not involve major conformational changes and has been suggested to be dominated by electrostatic interactions. We used Brownian dynamics simulations to investigate the mechanism of formation of the LmP-LmCytc complex. Our simulations confirm the importance of electrostatic interactions involving the negatively charged D211 residue at the LmP active site, and reveal a previously unrecognized role in complex formation for negatively charged residues in helix A of LmP. The crystal structure of the D211N mutant of LmP reported herein is essentially identical to that of wild-type LmP, reinforcing the notion that it is the loss of charge at the active site, and not a change in structure, that reduces the association rate of the D211N variant of LmP. The Brownian dynamics simulations further show that complex formation occurs via a "bind and crawl" mechanism, in which LmCytc first docks to a location on helix A that is far from the active site, forming an initial encounter complex, and then moves along helix A to the active site. An atomistic molecular dynamics simulation confirms the helix A binding site, and steady state activity assays and stopped-flow kinetics measurements confirm the role of helix A charges in the association mechanism.

"Bind and Crawl" Association Mechanism of Leishmania major Peroxidase and Cytochrome c Revealed by Brownian and Molecular Dynamics Simulations.,Fields JB, Hollingsworth SA, Chreifi G, Heyden M, Arce AP, Magana-Garcia HI, Poulos TL, Tobias DJ Biochemistry. 2015 Dec 3. PMID:26598276<ref>PMID:26598276</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5amm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ascorbate peroxidase 3D structures|Ascorbate peroxidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Leishmania major]]
[[Category: Arce AP]]
[[Category: Chreifi G]]
[[Category: Fields JB]]
[[Category: Heyden M]]
[[Category: Hollingsworth SA]]
[[Category: Magana-Garcia HI]]
[[Category: Poulos TL]]
[[Category: Tobias DJ]]