Alternate locations of backbones: Difference between revisions
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At sufficiently high [[resolution]], [[Empirical models|empirical methods]] for determining macromolecular structure may detect multiple locations for some atoms, termed [[alternate locations]]. When alternate locations for backbones (main chains) deviate substantially, the backbone may separate into two pathways ("fork") and then rejoin into a single pathway. | <table align="right" border="0" width="550" style="margin:0px 0px 0px 10px;"><tr><td> | ||
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[[Image:Altloc-anim-cartoon-5sop.gif]] | |||
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Animation of the alternate location 3 backbone [http://firstglance.jmol.org/conformations.htm conformations] of [[5sop]]: | |||
<br><big> | |||
<font color="red"><b>1</b></font> | |||
<font color="orange"><b>2</b></font> | |||
<font color="#00b000"><b>3</b></font>.</big><br> | |||
[http://firstglance.jmol.org/videocapture.htm Captured] from [[FirstGlance in Jmol]]. | |||
<span style="background-color:black;padding:3px 3px 0px 3px;font-weight:bold;"> | |||
<span style="color:white;">Common to all conformations. </span> | |||
<br> | |||
<span style="color:Pink;"> Pink</span></span>: [http://firstglance.jmol.org/notes.htm#singletons Singletons]. | |||
<br><br> | |||
This is a major oversimplification of [http://firstglance.jmol.org/notes.htm#conformations all possible conformations]. | |||
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At sufficiently high [[resolution]], [[Empirical models|empirical methods]] for determining macromolecular structure may detect multiple locations for some atoms, termed [[alternate locations]]. When alternate locations for backbones (main chains) deviate substantially, the backbone may separate into two pathways ("fork") and then rejoin into a single pathway. [[FirstGlance in Jmol]] can color each [http://firstglance.jmol.org/conformations.htm conformation] distinctly, animate them, and isolate each. [http://firstglance.jmol.org/fg.htm?mol=5sop Explore 5sop in FirstGlance in Jmol]. | |||
==Alternate location server== | ==Alternate location server== | ||
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ID Method Res Dep Date | ID Method Res Dep Date | ||
9ins X-ray diffraction 1.70 1991-10-23 min=-1.0 ave=-1.0 max=-1.0 A=48 B=48 | 9ins X-ray diffraction 1.70 1991-10-23 min=-1.0 ave=-1.0 max=-1.0 A=48 B=48 | ||
4dgd X-ray diffraction 1.4 2012-01-25 min=0.03 ave=4.78 max=15.87 A=84 B=84 A.CA=13 B.CA=13 | 4dgd X-ray diffraction 1.4 2012-01-25 min=0.03 ave=4.78 max=15.87 A=84 B=84 A.CA=13 B.CA=13 | ||
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===X-ray diffraction=== | ===X-ray diffraction=== | ||
Half of all X-ray diffraction entries have AltLocs, and ~90% of those have backbone atom AltLocs. | Half of all X-ray diffraction entries have AltLocs, and ~90% of those (~79,000) have backbone atom AltLocs. However, only 1,035 entries with backbone atom AltLocs (1.3%) have "substantial" '''maximum''' backbone atom AltLoc separations of >5.0 Å. | ||
<!--However, not quite ~500 entries (<1%) have "substantial" separations of some AltLoc backbone atoms, namely separations averaging >2.5 Å.--> | |||
(The [[van der Waals radii|van der Waals diameter]] of a carbon atom is 3.4 Å. | |||
The '''average''' separations for those 1,035 with maximum separations >5.0 Å range from 0.14 to 91 Å, with 184 entries having average separations >5.0 Å.) 3,560 entries have maximum separations ≥2.0 Å, and 6,125 ≥ 1.0 Å. | |||
{| class="wikitable" | {| class="wikitable" | ||
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{| class="wikitable" | {| class="wikitable" | ||
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| [https://www.uniprot.org/uniprotkb/B0LJC8/entry TRIMCyp protein] mediates innate immunity to HIV by inhibiting post-entry retrovirus replication. Evidence suggests that TRIMCyp has evolved through mutations to broaden the range of retroviruses it can inhibit<ref name="4dgd">PMID: 22407016</ref>. These mutations render the active site able to assume multiple conformations. In particular, the cyclophilin-binding loop 64-74 (GGNFT HCNGT GG), flanked by double glycine pivots, exhibited flexibility<ref name="4dgd" />. A crystal structure, [[4dgd]], resolved two alternate location conformations for the loop residues 66-74, shown at right in red (AltLoc A) and orange (AltLoc B), each at about 50% occupancy. | | [https://www.uniprot.org/uniprotkb/B0LJC8/entry TRIMCyp protein] mediates innate immunity to HIV by inhibiting post-entry retrovirus replication. Evidence suggests that TRIMCyp has evolved through mutations to broaden the range of retroviruses it can inhibit<ref name="4dgd">PMID: 22407016</ref>. These mutations render the active site able to assume multiple conformations. In particular, the cyclophilin-binding loop 64-74 (GGNFT HCNGT GG), flanked by double glycine pivots, exhibited flexibility<ref name="4dgd" />. A crystal structure, [[4dgd]], resolved two alternate location conformations for the loop residues 66-74, shown at right in '''{{Font color|red|red (AltLoc A)}}''' and '''{{Font color|orange|orange (AltLoc B)}}''', each at about 50% occupancy. | ||
Explore [http://firstglance.jmol.org/fg.htm?mol=4dgd 4DGD in FirstGlance in Jmol], which has [[Alternate_locations#Visualizing_alternate_locations|AltLoc visualization/animation capabilities]]. | Explore [http://firstglance.jmol.org/fg.htm?mol=4dgd 4DGD in FirstGlance in Jmol], which has [[Alternate_locations#Visualizing_alternate_locations|AltLoc visualization/animation capabilities]]. | ||
[[#Alternate location server|AltLoc Server Report]]: | [[#Alternate location server|AltLoc Server Report]]:<br> | ||
<tt>4dgd X-ray diffraction 1.4 2012-01-25 min=0.03 ave=4.78 max=15.87 A=84 B=84 A.CA=13 B.CA=13</tt> | <tt>4dgd X-ray diffraction 1.4 2012-01-25 min=0.03 ave=4.78 max=15.87 A=84 B=84 A.CA=13 B.CA=13</tt> | ||
| [[Image:4dgd-altlocs.png|right]] | | [[Image:4dgd-altlocs.png|right]] | ||
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Explore [http://firstglance.jmol.org/fg.htm?mol=2wlk 2WLK in FirstGlance in Jmol], which has [[Alternate_locations#Visualizing_alternate_locations|AltLoc visualization/animation capabilities]]. | Explore [http://firstglance.jmol.org/fg.htm?mol=2wlk 2WLK in FirstGlance in Jmol], which has [[Alternate_locations#Visualizing_alternate_locations|AltLoc visualization/animation capabilities]]. | ||
[[#Alternate location server|AltLoc Server Report]]: | [[#Alternate location server|AltLoc Server Report]]:<br> | ||
<tt>2wlk X-ray diffraction 2.8 2009-06-24 min=1.04 ave 5.64 max 9.99 A=1500 B=1540 A.CA=202 B.CA=206 | <tt>2wlk X-ray diffraction 2.8 2009-06-24 min=1.04 ave 5.64 max 9.99 A=1500 B=1540 A.CA=202 B.CA=206 | ||
</tt> | </tt> | ||
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| Selectivity filter domain of a single chain of the tetrameric pore. <b><span class="text-red">AltLoc A</span></b>, <b><span class="text-orange">AltLoc B</span></b>. | | Selectivity filter domain of a single chain of the tetrameric pore. <b><span class="text-red">AltLoc A</span></b>, <b><span class="text-orange">AltLoc B</span></b>. | ||
|} | |} | ||
====Additional Cases==== | |||
* [http://firstglance.jmol.org/fg.htm?mol=3pga 3PGA], a glutaminase-asparaginase, has a 20-residue flexible loop that is thought to orient substrate and help to transport substrate and product from the active site. | |||
* [http://firstglance.jmol.org/fg.htm?mol=3kqu 3KQU] illustrates a helicase ratchet translocation mechanism with its single-stranded DNA in four positions (conformations). | |||
* The [http://firstglance.jmol.org/fg.htm?mol=4myd&au=1 asymmetric unit of 4MYD] is a trimeric enzyme, in which "two [chains] bind one or both small molecule ligands and the third in the middle is present in two C2-symmetric conformations in a 1:1 ratio without any ligands." Here you will see alternate locations representing the entire middle chain rotated close to 180 degrees. | |||
* [http://firstglance.jmol.org/fg.htm?mol=6xkc 6XKC] is a hexamer. Two of the chains are modeled at two different angles relative to the other 4. In animation, these chains wave back and forth. | |||
==References== | ==References== | ||
<references /> | <references /> | ||