2OPH.A | DPP4 – ASTRID

2OPH.A | DPP4

General Structure Information

PDB ID	2oph
HGNC Gene Label(s)	DPP4
Structure Name	human dipeptidyl peptidase iv in complex with an alpha amino acid inhibitor
Resolution	2.4Å
Reference	AUTH J.L.DUFFY,B.A.KIRK,L.WANG,G.J.EIERMANN,H.HE,B.LEITING,AUTH 2 K.A.LYONS,R.A.PATEL,S.B.PATEL,A.PETROV,G.SCAPIN,J.K.WU,AUTH 3 N.A.THORNBERRY,A.E.WEBERTITL 4-AMINOPHENYLALANINE AND 4-AMINOCYCLOHEXYLALANINETITL 2 DERIVATIVES AS POTENT, SELECTIVE, AND ORALLY BIOAVAILABLETITL 3 INHIBITORS OF DIPEPTIDYL PEPTIDASE IV.REF BIOORG.MED.CHEM.LETT. V. 17 2879 2007REFN ISSN 0960-894XPMID 17350841DOI 10.1016/J.BMCL.2007.02.066

Variant Set Distributions

ExAC Variants

Number Of Residues	728
Number Of SNVs	178
Number Of Permutations	69524
Optimal Distance Threshold	7.0
K Statistic	0.011
p-value	0.922

COSMIC

Number Of Residues	728
Number Of SNVs	10
Number Of Permutations	8547
Optimal Distance Threshold	23.0
K Statistic	0.4
p-value	0.074

Ripley’s K Analysis Plots

ExACCOSMIC

Variant Set Comparisons

Cosmic vs. ExAC

Number Of ExAC SNVs	178
Number Of COSMIC SNVs	8
Optimal Distance Threshold	22.0
K Statistic	0.318
p-value	0.022

Mapped Variants

[+] ExAC Missense Variants

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
2:162903954	rs201575795	N>S	A:51	(36.78, 60.94, 59.44)
2:162903955		N>D	A:51	(36.78, 60.94, 59.44)
2:162903944	rs199566230	R>S	A:54	(41.55, 62.41, 61.61)
2:162903919	rs149517088	I>V	A:63	(62.51, 71.60, 44.72)
2:162903510		E>V	A:67	(65.67, 71.68, 49.03)
2:162903501		Y>C	A:70	(55.17, 69.56, 54.69)
2:162903495		Q>R	A:72	(53.28, 73.07, 58.51)
2:162903486	rs202227776	N>S	A:75	(52.37, 77.93, 55.79)
2:162903484	rs373370226	I>V	A:76	(54.79, 76.72, 51.55)
2:162903480		L>S	A:77	(57.79, 75.08, 54.91)
2:162903473	COSM461318	F>L	A:79	(61.89, 70.97, 55.05)
2:162903471		N>S	A:80	(67.94, 70.41, 54.20)
2:162903472		N>H	A:80	(67.94, 70.41, 54.20)
2:162903460	rs199929717 COSM1691219	G>R	A:84	(65.90, 69.35, 58.62)
2:162903439		E>K	A:91	(53.69, 83.61, 54.98)
2:162903432	rs544381314	S>N	A:93	(49.09, 85.69, 54.95)
2:162903433		S>R	A:93	(49.09, 85.69, 54.95)
2:162903429		T>I	A:94	(50.62, 86.13, 51.15)
2:162903426	rs143806961	F>S	A:95	(48.05, 84.81, 48.58)
2:162902122		D>N	A:96	(44.80, 87.00, 53.59)
2:162902097		D>G	A:104	(46.47, 73.73, 44.57)
2:162902087	rs200377808	I>M	A:107	(56.11, 76.36, 42.95)
2:162902086	rs202034264	S>A	A:108	(58.24, 77.37, 39.51)
2:162902078		D>E	A:110	(62.65, 78.79, 38.92)
2:162902080		D>N	A:110	(62.65, 78.79, 38.92)
2:162902057	rs145810986	E>D	A:117	(44.10, 75.80, 41.21)
2:162902055		Y>C	A:118	(40.88, 80.80, 40.92)
2:162902043	rs372129594 COSM3961368	K>T	A:122	(34.92, 66.94, 39.16)
2:162895663		D>V	A:133	(46.05, 84.02, 39.07)
2:162895661	rs199969667	I>V	A:134	(50.89, 84.00, 37.99)
2:162895655		D>H	A:136	(56.56, 87.57, 41.05)
2:162895648		N>S	A:138	(60.98, 87.68, 42.75)
2:162895646		K>E	A:139	(58.04, 91.35, 41.62)
2:162895529	rs201137953	Q>R	A:141	(53.45, 91.76, 41.74)
2:162895520		T>K	A:144	(47.81, 91.85, 36.02)
2:162895507		I>M	A:148	(45.83, 81.95, 32.54)
2:162895487		V>A	A:155	(48.36, 74.20, 33.65)
2:162895472		V>G	A:160	(63.39, 73.70, 33.62)
2:162895469		G>V	A:161	(61.99, 77.05, 34.99)
2:162895470	COSM1669333	G>R	A:161	(61.99, 77.05, 34.99)
2:162895466		H>R	A:162	(59.96, 80.77, 33.98)
2:162894911		I>V	A:172	(47.89, 73.89, 22.81)
2:162894892		P>Q	A:178	(54.74, 84.83, 33.31)
2:162894883	COSM1528604	P>Q	A:181	(52.04, 87.48, 25.28)
2:162894878		Y>N	A:183	(53.65, 82.53, 21.75)
2:162894862	rs147146003	T>M	A:188	(41.79, 72.21, 15.57)
2:162894859	rs137890810	G>E	A:189	(39.47, 73.07, 18.66)
2:162894835		G>E	A:197	(46.48, 68.23, 25.11)
2:162894827		D>H	A:200	(39.12, 61.20, 25.34)
2:162894817		Y>C	A:203	(43.17, 57.77, 25.04)
2:162894814		E>V	A:204	(40.77, 60.80, 31.56)
2:162891816	rs200357193 COSM139404	Y>C	A:211	(41.97, 66.62, 30.88)
2:162891814		S>P	A:212	(47.38, 65.61, 30.30)
2:162891789		G>D	A:220	(61.81, 72.97, 27.37)
2:162891757		T>P	A:231	(34.00, 62.72, 14.89)
2:162891748	rs140092320	P>A	A:234	(29.46, 57.00, 20.01)
2:162891727	rs372231467	Y>N	A:241	(17.77, 64.88, 37.45)
2:162891707	rs577626040	Q>H	A:247	(11.44, 73.70, 35.24)
2:162891708	rs201266487	Q>P	A:247	(11.44, 73.70, 35.24)
2:162891691	rs182689048	R>W	A:253	(24.42, 65.05, 25.23)
2:162891682		Y>H	A:256	(31.75, 55.69, 26.93)
2:162890147		P>L	A:264	(39.07, 57.43, 19.37)
2:162890142	rs56179129	V>I	A:266	(45.71, 59.37, 17.73)
2:162890137		K>N	A:267	(47.08, 62.74, 14.83)
2:162890129		V>A	A:270	(56.82, 67.88, 18.38)
2:162890118		D>Y	A:274	(63.06, 77.96, 21.97)
2:162890096		N>S	A:281	(50.93, 80.49, 13.03)
2:162890097	rs200439038	N>H	A:281	(50.93, 80.49, 13.03)
2:162890075		T>S	A:288	(53.71, 58.99, 11.95)
2:162890072	rs202159507	A>V	A:289	(52.64, 55.55, 13.40)
2:162890070	COSM207526	P>S	A:290	(53.98, 52.46, 13.29)
2:162890066	rs539922436	A>V	A:291	(52.71, 50.36, 9.72)
2:162890067		A>P	A:291	(52.71, 50.36, 9.72)
2:162890060	COSM1669332	M>T	A:293	(50.02, 50.11, 14.62)
2:162890061		M>V	A:293	(50.02, 50.11, 14.62)
2:162881448		D>N	A:297	(41.79, 50.48, 14.92)
2:162881433		D>N	A:302	(54.11, 55.79, 26.54)
2:162881409	rs375183248 COSM70525	R>G	A:310	(66.80, 60.14, 21.83)
2:162881406	rs200137356	I>V	A:311	(60.63, 61.09, 21.85)
2:162881387		R>K	A:317	(48.05, 46.07, 16.70)
2:162881360	rs144380286	D>G	A:326	(59.06, 54.32, 17.72)
2:162881346		D>H	A:331	(67.41, 66.42, 11.95)
2:162881328		W>R	A:337	(61.54, 64.89, 16.12)
2:162879306	rs148403324	R>W	A:343	(67.06, 53.59, 17.24)
2:162879299		H>R	A:345	(62.18, 48.04, 20.50)
2:162879296		I>T	A:346	(58.10, 44.33, 18.97)
2:162879297		I>V	A:346	(58.10, 44.33, 18.97)
2:162879289		M>I	A:348	(54.28, 39.98, 21.39)
2:162879281	rs200857741	T>I	A:351	(48.82, 34.39, 27.29)
2:162879282	COSM3837171	T>A	A:351	(48.82, 34.39, 27.29)
2:162879265		R>S	A:356	(50.87, 44.80, 35.59)
2:162877146		I>T	A:374	(58.54, 46.13, 33.79)
2:162877137		N>S	A:377	(59.40, 36.11, 32.28)
2:162877138	rs201505325	N>H	A:377	(59.40, 36.11, 32.28)
2:162877121		R>S	A:382	(54.97, 41.16, 34.66)
2:162877115		I>M	A:384	(63.75, 44.74, 35.38)
2:162877110		Y>C	A:386	(69.89, 47.00, 29.71)
2:162877105		Q>K	A:388	(70.86, 48.33, 24.33)
2:162877101		I>R	A:389	(68.39, 52.18, 21.44)
2:162877102		I>L	A:389	(68.39, 52.18, 21.44)
2:162877097		D>E	A:390	(70.57, 49.43, 18.56)
2:162877098		D>G	A:390	(70.57, 49.43, 18.56)
2:162877091		K>N	A:392	(65.42, 42.03, 18.95)
2:162876794	COSM3743945	I>V	A:397	(68.16, 42.82, 35.78)
2:162876784		G>V	A:400	(61.40, 34.98, 39.87)
2:162876772	rs199887205	V>G	A:404	(58.87, 44.16, 39.53)
2:162876766	rs200764195	G>E	A:406	(58.46, 49.29, 39.84)
2:162876764		I>L	A:407	(61.27, 51.20, 37.65)
2:162876755	rs138404587	L>V	A:410	(68.26, 55.02, 37.04)
2:162876739		L>P	A:415	(67.52, 50.12, 39.26)
2:162875781	rs377513691	Y>C	A:417	(63.50, 46.88, 42.51)
2:162875767	rs201969016	Y>H	A:422	(60.72, 40.04, 52.73)
2:162875743	rs377339779	N>Y	A:430	(59.70, 45.99, 50.02)
2:162875736		Y>C	A:432	(64.18, 45.29, 46.87)
2:162875733		K>T	A:433	(70.06, 48.90, 45.85)
2:162875734		K>E	A:433	(70.06, 48.90, 45.85)
2:162875358		I>N	A:434	(70.13, 46.15, 41.05)
2:162875349	rs1129599	S>T	A:437	(77.96, 45.98, 37.70)
2:162875331		T>I	A:443	(70.10, 45.56, 48.46)
2:162875309		N>K	A:450	(59.57, 47.81, 61.51)
2:162875278	rs200042124	F>L	A:461	(63.93, 58.27, 45.06)
2:162875268	rs201558355	E>G	A:464	(69.64, 63.48, 40.59)
2:162875262		K>M	A:466	(71.58, 62.86, 47.04)
2:162875263		K>E	A:466	(71.58, 62.86, 47.04)
2:162875256		Y>S	A:468	(65.54, 56.82, 50.07)
2:162875253	rs200729319	Q>L	A:469	(59.57, 59.71, 51.33)
2:162875239	rs201959805	G>R	A:474	(51.89, 48.23, 56.65)
2:162873638		H>R	A:483	(65.87, 57.17, 54.02)
2:162873632		S>N	A:485	(71.36, 57.06, 48.74)
2:162873623		D>G	A:488	(71.22, 53.29, 52.32)
2:162873618		G>R	A:490	(68.49, 57.00, 58.42)
2:162873370	rs17848907 COSM717233	R>T	A:492	(65.20, 62.95, 59.32)
2:162873356		N>D	A:497	(50.69, 58.22, 62.91)
2:162873344		D>H	A:501	(48.94, 54.62, 68.75)
2:162873330	rs199655514	Q>H	A:505	(45.86, 52.74, 73.20)
2:162873318		M>I	A:509	(40.73, 48.16, 66.77)
2:162873313		S>F	A:511	(42.52, 41.75, 63.53)
2:162873306		K>N	A:513	(44.50, 35.96, 59.08)
2:162873278	rs200675520	K>E	A:523	(49.96, 29.60, 47.10)
2:162870961	rs200348396	M>V	A:528	(40.08, 37.03, 57.45)
2:162870911	rs144500430	L>F	A:544	(33.24, 38.00, 50.51)
2:162870913	rs200385525 COSM1008331	L>I	A:544	(33.24, 38.00, 50.51)
2:162868467	rs373721374	D>E	A:556	(46.88, 43.82, 51.40)
2:162868441		T>I	A:565	(36.89, 48.54, 60.66)
2:162868435		L>P	A:567	(31.24, 45.59, 59.79)
2:162868436		L>V	A:567	(31.24, 45.59, 59.79)
2:162868424	rs369643133	E>K	A:571	(28.17, 44.75, 64.15)
2:162868413		I>M	A:574	(34.45, 37.73, 59.58)
2:162868378	rs577060626	Q>R	A:586	(50.25, 36.29, 41.69)
2:162868351		N>S	A:595	(42.15, 35.94, 28.19)
2:162868339		G>E	A:599	(32.96, 35.73, 34.46)
2:162868319		Q>K	A:606	(35.48, 34.79, 45.22)
2:162868310		A>T	A:609	(36.60, 30.68, 49.16)
2:162868303		R>K	A:611	(32.46, 26.17, 48.59)
2:162865804		Q>K	A:612	(37.59, 26.50, 51.50)
2:162865798		S>P	A:614	(32.16, 27.49, 55.44)
2:162865790		M>I	A:616	(36.83, 27.55, 58.47)
2:162865788	rs199554489	G>E	A:617	(34.74, 26.89, 62.86)
2:162865770	rs147614497	R>Q	A:623	(25.18, 34.55, 60.08)
2:162865760		I>M	A:626	(28.93, 38.93, 48.60)
2:162865762	rs200298322	I>V	A:626	(28.93, 38.93, 48.60)
2:162865759		W>G	A:627	(30.78, 45.05, 49.54)
2:162865168		Y>H	A:631	(35.11, 43.39, 37.95)
2:162865161		G>E	A:633	(29.45, 44.03, 41.49)
2:162865162		G>R	A:633	(29.45, 44.03, 41.49)
2:162865156	rs200430209 COSM329327	V>I	A:635	(31.75, 39.31, 40.91)
2:162865152		T>I	A:636	(28.58, 40.21, 43.86)
2:162865143		V>A	A:639	(28.05, 34.99, 42.98)
2:162865134	rs200839327	S>L	A:642	(25.48, 30.92, 40.83)
2:162865127	rs201712012	S>R	A:644	(25.87, 28.27, 45.19)
2:162865123		V>M	A:646	(27.15, 29.72, 49.76)
2:162865113		C>Y	A:649	(23.21, 38.13, 51.23)
2:162865111		G>R	A:650	(23.94, 40.97, 48.70)
2:162865102		V>M	A:653	(27.78, 49.26, 44.27)
2:162865098	rs149643982	A>V	A:654	(28.10, 50.16, 40.33)
2:162865099		A>T	A:654	(28.10, 50.16, 40.33)
2:162865089		S>C	A:657	(25.65, 44.00, 33.49)
2:162865086	rs138430103	R>Q	A:658	(25.63, 43.18, 28.25)
2:162865087		R>W	A:658	(25.63, 43.18, 28.25)
2:162862307	rs373101146	T>R	A:667	(36.22, 45.49, 27.62)
2:162862301		R>H	A:669	(42.73, 45.62, 28.12)
2:162862302	rs199925807	R>C	A:669	(42.73, 45.62, 28.12)
2:162862290	rs367803685	L>V	A:673	(36.15, 42.51, 19.22)
2:162862287		P>S	A:674	(31.91, 42.28, 20.17)
2:162862284	rs201306777	T>A	A:675	(32.40, 39.92, 16.77)
2:162851876	rs200726335	T>A	A:687	(25.26, 38.46, 31.36)
2:162851868		M>I	A:689	(20.98, 40.26, 32.79)
2:162851870		M>V	A:689	(20.98, 40.26, 32.79)
2:162851843	COSM717236	V>I	A:698	(19.20, 35.54, 47.24)
2:162851539	rs199667955	V>I	A:711	(29.35, 52.12, 35.25)
2:162851524		S>T	A:716	(21.61, 48.61, 37.04)
2:162851514	rs142229257	I>N	A:719	(20.20, 44.12, 36.75)
2:162851515		I>F	A:719	(20.20, 44.12, 36.75)
2:162851506	rs142600908	A>T	A:722	(15.56, 41.02, 34.72)
2:162851500		V>I	A:724	(10.96, 42.44, 37.19)
2:162851497	COSM1204492	D>N	A:725	(11.05, 40.29, 33.55)
2:162851473		M>V	A:733	(18.91, 53.12, 46.56)
2:162849892	rs145529637	W>C	A:734	(16.91, 56.32, 43.19)
2:162849882		E>K	A:738	(26.17, 60.89, 43.02)
2:162849869		I>R	A:742	(28.58, 57.29, 45.48)
2:162849870		I>L	A:742	(28.58, 57.29, 45.48)
2:162849850		H>Q	A:748	(30.09, 58.11, 52.16)
2:162849809	rs144519975	C>S	A:762	(21.02, 39.26, 56.68)
2:162849798		P>S	A:766	(21.16, 43.95, 66.94)

Position	Variant	AA Change	PDB Chain Position	Structure Coordinates
2:162891790	COSM570525	G>S	A:220	(61.81, 72.97, 27.37)
2:162890060	COSM1669332	M>T	A:293	(50.02, 50.11, 14.62)
2:162881402	COSM1008338	S>Y	A:312	(59.62, 57.37, 23.39)
2:162881323	COSM4136495	N>K	A:338	(63.79, 60.86, 12.08)
2:162879287	COSM3708996	S>N	A:349	(51.07, 38.30, 24.35)
2:162877183	COSM1669330	P>S	A:362	(60.40, 53.62, 29.46)
2:162875265	COSM441318	A>V	A:465	(68.65, 59.90, 43.93)
2:162868418	COSM1631378	I>V	A:573	(30.91, 41.02, 60.83)
2:162868384	COSM4969280	G>A	A:584	(47.97, 40.05, 40.68)
2:162865770	COSM1008327	R>Q	A:623	(25.18, 34.55, 60.08)

2OPH.A | DPP4.

2OPH.A | DPP4

General Structure Information

Variant Set Distributions

Ripley’s K Analysis Plots

Variant Set Comparisons

Mapped Variants

[+] ExAC Missense Variants

[+] COSMIC Missense Variants