title: Prediction of distal residue participation in enzyme catalysis.
abstract: A scoring method for the prediction of catalytically important residues in enzyme structures is presented and used to examine the participation of distal residues in enzyme catalysis. Scores are based on the Partial Order Optimum Likelihood (POOL) machine learning method, using computed electrostatic properties, surface geometric features, and information obtained from the phylogenetic tree as input features. Predictions of distal residue participation in catalysis are compared with experimental kinetics data from the literature on variants of the featured enzymes; some additional kinetics measurements are reported for variants of Pseudomonas putida nitrile hydratase (ppNH) and for Escherichia coli alkaline phosphatase (AP). The multilayer active sites of P. putida nitrile hydratase and of human phosphoglucose isomerase are predicted by the POOL log ZP scores, as is the single-layer active site of P. putida ketosteroid isomerase. The log ZP score cutoff utilized here results in over-prediction of distal residue involvement in E. coli alkaline phosphatase. While fewer experimental data points are available for P. putida mandelate racemase and for human carbonic anhydrase II, the POOL log ZP scores properly predict the previously reported participation of distal residues.
authors: Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, 02115; Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts, 02454-9110; Department of Chemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts, 02454-9110.
authors: Heather R
authors: HR
authors: Brodkin
authors: Nicholas A
authors: NA
authors: DeLateur
authors: Srinivas
authors: S
authors: Somarowthu
authors: Caitlyn L
authors: CL
authors: Mills
authors: Walter R
authors: WR
authors: Novak
authors: Penny J
authors: PJ
authors: Beuning
authors: Dagmar
authors: D
authors: Ringe
authors: Mary Jo
authors: MJ
authors: Ondrechen
mesh_terms: D024402:Carbonic Anhydrase II / Q000737:chemistry* / Q000235:genetics; D002384:Catalysis; D004798:Enzymes / Q000737:chemistry* / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D000069550:Machine Learning; D010802:Phylogeny; D011487:Protein Conformation; D016958:Pseudomonas putida / Q000201:enzymology; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D004798:Enzymes; D024402:Carbonic Anhydrase II; D005956:Glucose-6-Phosphate Isomerase
keywords: alkaline phosphatase; catalytic efficiency; ketosteroid isomerase; nitrile hydratase; partial order optimum likelihood; phosphoglucose isomerase; remote residues
references: Annu Rev Biophys Biomol Struct. 1992;21:441-83
references: 1525473
references: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D129-33
references: 14681376
references: Protein Eng. 1991 Oct;4(7):801-4
references: 1798702
references: Proteins. 1988;4(4):274-82
references: 3151019
references: Environ Mol Mutagen. 2012 Dec;53(9):766-76
references: 23034734
references: J Mol Biol. 2004 Sep 17;342(3):847-60
references: 15342241
references: Nature. 1988 Mar 31;332(6163):454-5
references: 3352744
references: Blood. 1996 Jun 1;87(11):4502-6
references: 8639816
references: FEBS Lett. 2001 Jun 15;499(1-2):11-4
references: 11418102
references: Biochim Biophys Acta. 2003 Jun 26;1649(1):68-73
references: 12818192
references: Bioinformatics. 2008 Nov 1;24(21):2445-52
references: 18776193
references: J Mol Biol. 1996 Apr 5;257(3):700-15
references: 8648634
references: Bioinformatics. 1999 Apr;15(4):327-32
references: 10320401
references: Biochemistry. 1997 Dec 16;36(50):15780-91
references: 9398308
references: Biochemistry. 2009 Jul 28;48(29):6932-9
references: 19469568
references: Blood Cells Mol Dis. 1997 Dec;23(3):402-9
references: 9446754
references: Biochemistry. 2008 Jul 22;47(29):7663-72
references: 18627128
references: Biochemistry. 1995 Mar 7;34(9):2788-97
references: 7893690
references: Nature. 1988 Mar 31;332(6163):455-7
references: 3352745
references: Biosci Biotechnol Biochem. 2006 Apr;70(4):881-9
references: 16636455
references: Biochemistry. 2011 Jun 7;50(22):4923-35
references: 21473592
references: Biochemistry. 1995 Mar 7;34(9):2777-87
references: 7893689
references: Nucleic Acids Res. 2009 Jan;37(Database issue):D588-92
references: 18984617
references: Protein Sci. 1994 Nov;3(11):2005-14
references: 7703848
references: Science. 2014 Dec 19;346(6216):1510-4
references: 25525245
references: Annu Rev Biochem. 1999;68:33-57
references: 10872443
references: Biochemistry. 1991 Aug 6;30(31):7789-96
references: 1907846
references: Biochemistry. 1968 Jul;7(7):2554-62
references: 4298222
references: Am J Hum Genet. 1991 Nov;49(5):1082-90
references: 1928091
references: Proteins. 2005 May 1;59(2):183-95
references: 15739204
references: J Mol Biol. 1998 Apr 3;277(3):647-62
references: 9533886
references: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references: 10592235
references: Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12473-8
references: 11606719
references: J Bacteriol. 1995 May;177(9):2602-5
references: 7730300
references: Biochemistry. 1997 Nov 18;36(46):14030-6
references: 9369474
references: Eur J Biochem. 1998 Oct 15;257(2):500-5
references: 9826199
references: Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9122-6
references: 15967977
references: J Inorg Biochem. 2002 Jul 25;91(1):70-7
references: 12121763
references: Biochemistry. 2014 Nov 4;53(43):6811-9
references: 25299936
references: Biochemistry. 2000 Apr 25;39(16):4581-9
references: 10769113
references: Chembiochem. 2001 Aug 3;2(7-8):517-23
references: 11828484
references: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W27-32
references: 17488835
references: Bioinformatics. 2012 Aug 1;28(15):2078-9
references: 22661648
references: Biochemistry. 1992 Sep 8;31(35):8196-200
references: 1525159
references: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1960-5
references: 20080683
references: Biochemistry. 1988 Nov 1;27(22):8338-43
references: 3072019
references: BMC Bioinformatics. 2007 Apr 09;8:119
references: 17419878
references: Biochemistry. 1999 Oct 19;38(42):13810-9
references: 10529226
references: Annu Rev Biochem. 2013;82:447-70
references: 23746259
references: Biochemistry. 1998 Jun 9;37(23):8325-30
references: 9622484
references: Biochemistry. 2010 Dec 7;49(48):10339-48
references: 21049962
references: J Bacteriol. 1997 Dec;179(24):7742-7
references: 9401033
references: Biochemistry. 1991 Sep 24;30(38):9264-73
references: 1892834
references: Protein Eng. 1995 Sep;8(9):865-71
references: 8746724
references: Biochemistry. 2011 Nov 1;50(43):9283-95
references: 21970785
references: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14271-5
references: 19706511
references: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13761-6
references: 16172409
references: Curr Protoc Bioinformatics. 2004 Sep;Chapter 8:Unit 8.6
references: 18428736
references: Chem Rev. 2011 Dec 14;111(12):7595-624
references: 21923192
references: PLoS Biol. 2006 Apr;4(4):e99
references: 16602823
references: Curr Opin Microbiol. 2006 Jun;9(3):261-7
references: 16621678
references: Biochemistry. 2005 Apr 12;44(14):5444-52
references: 15807537
references: Trends Biochem Sci. 1999 Jan;24(1):8-11
references: 10087914
references: J Mol Biol. 2000 Dec 8;304(4):645-56
references: 11099386
references: Protein Sci. 1995 Aug;4(8):1498-506
references: 8520475
references: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W39-43
references: 15980496
references: Biochemistry. 1996 May 7;35(18):5662-9
references: 8639525
references: J Biol Chem. 2004 Aug 6;279(32):33492-500
references: 15169773
references: Cancer Res. 1996 Jul 1;56(13):2960-3
references: 8674049
references: Eur J Biochem. 2004 Jan;271(2):429-38
references: 14717710
references: J Mol Biol. 2001 Jun 1;309(2):447-63
references: 11371164
references: ACS Chem Biol. 2009 Apr 17;4(4):269-73
references: 19260691
references: Biopolymers. 2011 Jun;95(6):390-400
references: 21254002
references: Biochemistry. 1994 Mar 1;33(8):2279-84
references: 8117685
references: J Mol Biol. 1991 Mar 20;218(2):449-64
references: 2010919
references: Biochemistry. 2001 Nov 13;40(45):13529-37
references: 11695900
references: Eur J Biochem. 1993 Feb 1;211(3):821-7
references: 8436138
references: Endocr Relat Cancer. 2004 Dec;11(4):749-59
references: 15613449
references: Nat Biotechnol. 1998 Aug;16(8):733-6
references: 9702770
references: Biochemistry. 2007 Feb 13;46(6):1466-76
references: 17279612
references: J Biol Chem. 1999 Jan 22;274(4):2344-9
references: 9891001
references: Nucleic Acids Res. 2009 Jul;37(Web Server issue):W390-5
references: 19443452
references: Biochemistry. 2000 Feb 8;39(5):955-64
references: 10653639
references: Biochemistry. 1991 Sep 24;30(38):9274-81
references: 1909893
references: Protein Sci. 2005 Mar;14(3):727-34
references: 15689508
references: Biochemistry. 2009 Nov 10;48(44):10608-19
references: 19799395
references: PLoS Comput Biol. 2009 Jan;5(1):e1000266
references: 19148270
references: Biochemistry. 1993 Sep 28;32(38):9896-900
references: 8399158
references: Biochemistry. 1993 Sep 28;32(38):9901-5
references: 8399159
references: PLoS Comput Biol. 2009 Dec;5(12):e1000585
references: 19997483
references: J Inorg Biochem. 2001 Feb;83(4):247-53
references: 11293544