omega loop

Omega loops, being non-regular, non-repeating secondary structural units, have a variety of three-dimensional shapes. Omega loop shapes are analyzed to identify recurring patterns in dihedral angles and overall loop shape to help identify potential roles in protein folding and function.{{cite journal|last1=Pal|first1=M|last2=Dasgupta|first2=S|title=The nature of the turn in omega loops of proteins|journal=Proteins|date=1 Jun 2003|volume=51|issue=4|pages=591–606|pmid=12784218|doi=10.1002/prot.10376|s2cid=44815936}}{{cite journal|last1=Dhar|first1=J|last2=Chakrabarti|first2=P|title=Defining the loop structures in proteins based on composite β-turn mimics|journal=Protein Eng Des Sel|date=Jun 2015|volume=28|issue=6|pages=153–61|doi=10.1093/protein/gzv017|pmid=25870305|doi-access=free}}

Since loops are almost always at the protein surface, it is often assumed that these structures are flexible; however, different omega loops exhibit ranges of flexibility across different time scales of protein motion and have been identified as playing a role in the folding of some proteins, including HIV-1 reverse transcriptase;{{cite journal|last1=Mager|first1=PP|title=Molecular simulation of the folding patterns of the omega-loop (Tyr181 to Tyr188) of HIV-1 reverse transcriptase|journal=Drug des Discov|date=Dec 1996|volume=14|issue=3|pages=213–23|pmid=9017364}}{{cite journal|last1=Mager|first1=PP|last2=Walther|first2=H|title=A hydrophilic omega-loop (Tyr181 to Tyr188) in the nonsubstrate binding area of HIV-1 reverse transcriptase|journal=Drug des Discov|date=Dec 1996|volume=14|issue=3|pages=225–39|pmid=9017365}} cytochrome c;{{cite journal|last1=Maity|first1=H|last2=Rumbley|first2=JN|last3=Englander|first3=SW|title=Functional role of a protein foldon--an Omega-loop foldon controls the alkaline transition in ferricytochrome c|journal=Proteins|date=1 May 2006|volume=63|issue=2|pages=349–55|pmid=16287119|doi=10.1002/prot.20757|citeseerx=10.1.1.596.3784|s2cid=38183696}}{{cite journal|last1=Caroppi|first1=P|last2=Sinibaldi|first2=F|last3=Santoni|first3=E|last4=Howes|first4=BD|last5=Fiorucci|first5=L|last6=Ferri|first6=T|last7=Ascoli|first7=F|last8=Smulevich|first8=G|last9=Santucci|first9=R|title=The 40s Omega-loop plays a critical role in the stability and the alkaline conformational transition of cytochrome c|journal=J Biol Inorg Chem|date=Dec 2004|volume=9|issue=8|pages=997–1006|pmid=15503233|doi=10.1007/s00775-004-0601-9|hdl=2108/34631|s2cid=2130725|hdl-access=free}} and nucleases.{{cite journal|last1=Vu|first1=ND|last2=Feng|first2=H|last3=Bai|first3=Y|title=The folding pathway of barnase: the rate-limiting transition state and a hidden intermediate under native conditions|date=30 Mar 2004|journal=Biochemistry|volume=43|issue=12|pages=3346–56|pmid=15035606|doi=10.1021/bi0362267}}{{cite journal|last1=Wang|first1=X|last2=Wang|first2=M|last3=Tong|first3=Y|last4=Shan|first4=L|last5=Wang|first5=J|title=Probing the folding capacity and residual structures in 1-79 residues fragment of staphylococcal nuclease by biophysical and NMR methods|journal=Biochimie|date=Oct 2006|volume=88|issue=10|pages=1343–55|pmid=17045725|doi=10.1016/j.biochi.2006.05.002}}

Omega loops can contribute to protein function. For example, omega loops can help stabilize interactions between protein and ligand, such as in the enzyme triose phosphate isomerase,{{cite journal|last1=Xiang|first1=J|last2=Jung|first2=JY|last3=Sampson|first3=NS|title=Entropy effects on protein hinges: the reaction catalyzed by triosephosphate isomerase|journal=Biochemistry|date=14 Sep 2004|volume=43|issue=36|pages=11436–45|doi=10.1021/bi049208d|pmid= 15350130}} and can directly affect protein function in other enzymes.{{cite journal|last1=Neuhaus|first1=FC|title=Role of the omega loop in specificity determination in subsite 2 of the D-alanine:D-alanine (D-lactate) ligase from Leuconostoc mesenteroides: a molecular docking study|journal=J Mol Graph Model|date=Sep 2011|volume=30|pages=31–7|doi=10.1016/j.jmgm.2011.06.002|pmid= 21727015}}{{cite journal|last1=Sampson|first1=NS|last2=Kass|first2=IJ|last3=Ghoshroy|first3=KB|title=Assessment of the role of an omega loop of cholesterol oxidase: a truncated loop mutant has altered substrate specificity|journal=Biochemistry|date=21 Apr 1998|volume=37|issue=16|pages=5770–8|pmid= 9548964|doi=10.1021/bi973067g}} A heritable coagulation disorder is caused by a single-site mutation in an omega loop of protein C.{{cite journal|last1=Preston|first1=RJ|last2=Morse|first2=C|last3=Murden|first3=SL|last4=Brady|first4=SK|last5=O'Donnell|first5=JS|last6=Mumford|first6=AD|title=The protein C omega-loop substitution Asn2Ile is associated with reduced protein C anticoagulant activity|journal=Br J Haematol|date=Mar 2009|volume=144|issue=6|pages=946–53|doi=10.1111/j.1365-2141.2008.07550.x|pmid= 19133979|s2cid=1618500|doi-access=}}

Likewise, omega loops play an interesting role in the function of the beta-lactamases: mutations in the "omega loop region" of a beta-lactamase can change its specific function and substrate profile,{{cite journal|last1=Levitt|first1=PS|last2=Papp-Wallace|first2=KM|last3=Taracila|first3=MA|last4=Hujer|first4=AM|last5=Winkler|first5=ML|last6=Smith|first6=KM|last7=Xu|first7=Y|last8=Harris|first8=ME|last9=Bonomo|first9=RA|title=Exploring the role of a conserved class A residue in the Ω-Loop of KPC-2 β-lactamase: a mechanism for ceftazidime hydrolysis|journal=J Biol Chem|date=14 Sep 2013|volume=287|issue=38|pages=31783–93|doi=10.1074/jbc.M112.348540|pmid=22843686|pmc=3442512|doi-access=free}}{{cite journal|last1=Stojanoski|first1=V|last2=Chow|first2=DC|last3=Hu|first3=L|last4=Sankaran|first4=B|last5=Gilbert|first5=HF|last6=Prasad|first6=BV|last7=Palzkill|first7=T|title=A triple mutant in the Ω-loop of TEM-1 β-lactamase changes the substrate profile via a large conformational change and an altered general base for catalysis|journal=J Biol Chem|date=17 Apr 2015|volume=290|issue=16|pages=10382–94|doi=10.1074/jbc.M114.633438|pmid=25713062|pmc=4400348|doi-access=free}}{{cite journal|last1=Dutta|first1=M|last2=Kar|first2=D|last3=Bansal|first3=A|last4=Chakraborty|first4=S|last5=Ghosh|first5=AS|title=A single amino acid substitution in the Ω-like loop of E. coli PBP5 disrupts its ability to maintain cell shape and intrinsic beta-lactam resistance|journal=Microbiology|date=Apr 2015|volume=161|issue=Pt 4|pages=895–902|doi=10.1099/mic.0.000052|pmid=25667006|doi-access=free}} perhaps due to an important functional role of the correlated dynamics of the region.{{cite journal|last1=Brown|first1=JR|last2=Livesay|first2=DR|title=Flexibility Correlation between Active Site Regions Is Conserved across Four AmpC β-Lactamase Enzymes|journal=PLOS ONE|date=27 May 2015|volume=10|issue=5|page=e0125832|doi=10.1371/journal.pone.0125832|pmid=26018804|pmc=4446314|bibcode=2015PLoSO..1025832B|doi-access=free}}

Omega loops have long been recognized also for their importance in the function and folding of the protein cytochrome c, contributing both key functional residues and well as important dynamic properties.{{cite journal|last1=McClelland|first1=LJ|last2=Seagraves|first2=SM|last3=Khan|first3=MK|last4=Cherney|first4=MM|last5=Bandi|first5=S|last6=Culbertson|first6=JE|last7=Bowler|first7=BE|title=The response of Ω-loop D dynamics to truncation of trimethyllysine 72 of yeast iso-1-cytochrome c depends on the nature of loop deformation|journal=J Biol Inorg Chem|date=Jul 2015|volume=20|issue=5|pages=805–19|doi=10.1007/s00775-015-1267-1|pmid=25948392|pmc=4485566}}{{cite journal|last1=Krishna|first1=MM|last2=Lin|first2=Y|last3=Rumbley|first3=JN|last4=Englander|first4=SW|title=Cooperative omega loops in cytochrome c: role in folding and function|journal=J Mol Biol|date=1 Aug 2003|volume=331|issue=1|pages=29–36|pmid=12875833|doi=10.1016/s0022-2836(03)00697-1}}{{cite journal|last1=Fetrow|first1=JS|last2=Dreher|first2=U|last3=Wiland|first3=DJ|last4=Schaak|first4=DL|last5=Boose|first5=TL|title=Mutagenesis of histidine 26 demonstrates the importance of loop-loop and loop-protein interactions for the function of iso-1-cytochrome c|journal=Protein Sci|date=Apr 1998|volume=7|issue=4|pages=994–1005|pmid=9568906|doi=10.1002/pro.5560070417|pmc=2143970}} Many researchers have studied omega loop function and dynamics in specific protein systems using a so-called "loop swap" approach, in which loops are swapped between (usually) homologous proteins.{{cite journal|last1=Takehara|first1=S|last2=Onda|first2=M|last3=Zhang|first3=J|last4=Nishiyama|first4=M|last5=Yang|first5=X|last6=Mikami|first6=B|last7=Lomas|first7=DA|title=The 2.1-A crystal structure of native neuroserpin reveals unique structural elements that contribute to conformational instability|date=24 Apr 2009|journal=J Mol Biol|volume=388|issue=1|pages=11–20|doi=10.1016/j.jmb.2009.03.007|pmid=19285087}}{{cite journal|last1=Murphy|first1=ME|last2=Fetrow|first2=JS|last3=Burton|first3=RE|last4=Brayer|first4=GD|title=The structure and function of omega loop A replacements in cytochrome c|journal=Protein Sci|date=Sep 1993|volume=2|issue=9|pages=1429–40|pmid=8401228|doi=10.1002/pro.5560020907|pmc=2142463}}{{cite journal|last1=Fetrow|first1=JS|last2=Cardillo|first2=TS|last3=Sherman|first3=F|title=Deletions and replacements of omega loops in yeast iso-1-cytochrome c|journal=Proteins|date=1989|volume=6|issue=4|pages=372–81|pmid=2560195|doi=10.1002/prot.340060404|s2cid=25525703}}

{{Reflist|35em}}

Category:Protein structural motifs